Pub Date : 2024-10-01Epub Date: 2024-07-22DOI: 10.17925/EE.2024.20.2.12
Si Wei David Fan, Leong Tung Ong
Objectives: Hyperthyroidism has a significant impact on the cardiovascular system, causing thyrotoxic cardiomyopathy, which is characterized by atrial fibrillation, left ventricular hypertrophy and diastolic dysfunction, and may lead to heart failure. This study aimed to investigate the prevalence and associated risk factors for heart failure in patients with hyperthyroidism. Methods: A systematic literature search was conducted on PubMed, SCOPUS and Ovid SP up until April 2023. Pooled prevalence and pooled odds ratio for risk factors were calculated using the generic inverse variance method. Results: Studies involving 30,889 patients were included in this meta-analysis. The overall prevalence of heart failure in patients with hyperthyroidism was 8% (95% confidence interval [CI]: 6-11%). Further analyses revealed that the prevalence of heart failure in patients who underwent treatment with radioactive iodine ablation, antithyroid medication and thyroidectomy was 8% (95% CI: -1 to 16%), 6% (95% CI: 2 to 11%) and 4% (95% CI: -2 to 10%), respectively. The risk factors of heart failure in hyperthyroidism include atrial fibrillation, chronic kidney disease, anaemia, hypertension, history of stroke or transient ischaemic attack, history of coronary artery disease and diabetes mellitus. Conclusion: Heart failure occurs in 8% of patients with hyperthyroidism, with the most common risk factor being atrial fibrillation.
{"title":"Prevalence and Risk Factors of Heart Failure in Patients Diagnosed with Hyperthyroidism: A Systematic Review and Meta-analysis.","authors":"Si Wei David Fan, Leong Tung Ong","doi":"10.17925/EE.2024.20.2.12","DOIUrl":"10.17925/EE.2024.20.2.12","url":null,"abstract":"<p><p><b>Objectives:</b> Hyperthyroidism has a significant impact on the cardiovascular system, causing thyrotoxic cardiomyopathy, which is characterized by atrial fibrillation, left ventricular hypertrophy and diastolic dysfunction, and may lead to heart failure. This study aimed to investigate the prevalence and associated risk factors for heart failure in patients with hyperthyroidism. <b>Methods:</b> A systematic literature search was conducted on PubMed, SCOPUS and Ovid SP up until April 2023. Pooled prevalence and pooled odds ratio for risk factors were calculated using the generic inverse variance method. <b>Results:</b> Studies involving 30,889 patients were included in this meta-analysis. The overall prevalence of heart failure in patients with hyperthyroidism was 8% (95% confidence interval [CI]: 6-11%). Further analyses revealed that the prevalence of heart failure in patients who underwent treatment with radioactive iodine ablation, antithyroid medication and thyroidectomy was 8% (95% CI: -1 to 16%), 6% (95% CI: 2 to 11%) and 4% (95% CI: -2 to 10%), respectively. The risk factors of heart failure in hyperthyroidism include atrial fibrillation, chronic kidney disease, anaemia, hypertension, history of stroke or transient ischaemic attack, history of coronary artery disease and diabetes mellitus. <b>Conclusion:</b> Heart failure occurs in 8% of patients with hyperthyroidism, with the most common risk factor being atrial fibrillation.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 2","pages":"91-99"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. Obeticholic acid (OCA) has emerged as a promising drug in the management of nonalcoholic fatty liver disease (NAFLD). This meta-analysis aimed to analyse the therapeutic effect of OCA on NAFLD. Methods. Randomized controlled trials (RCTs) involving patients with NAFLD receiving OCA in the intervention arm and placebo in the control arm were searched throughout the electronic databases. The primary outcomes were changes in non-invasive markers of hepatic fibrosis and liver histology. The secondary outcomes included changes in liver enzymes, metabolic parameters from baseline and adverse events (AEs). Results. Four RCTs involving 1,278 subjects met the inclusion criteria. Over 6 weeks to 18 months of clinical use, OCA outperformed placebo in resolving definite nonalcoholic steatohepatitis (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.04-2.48], p=0.03) and improving fibrosis (OR 2.23, 95% CI [1.56-3.20], p<0.0001), hepatocellular ballooning (OR 1.83, 95% CI [1.35-2.47], p<0.0001) and lobular inflammation (OR 1.62, 95% CI [1.13-2.32], p=0.009). OCA did not improve the enhanced liver fibrosis score and steatosis better than placebo, and demonstrated superior efficacy compared with the placebo in reducing serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase levels. Although a favourable effect of OCA over placebo was seen in body-weight reduction, the OCA use was associated with adverse changes in lipid parameters. Except for the greater risk of pruritus and constipation, the AE profile was comparable between the OCA and placebo groups. Conclusions. OCA has a favourable efficacy in improving liver histology and liver enzymes. However, the worsening of lipid parameters and other AEs with the OCA use warrants further investigation.
{"title":"Role of Obeticholic Acid, a Farnesoid X Receptor Agonist, in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.","authors":"Abm Kamrul-Hasan, Sunetra Mondal, Lakshmi Nagendra, Thanikai Sasikanth, Afsar Ahammed, Shahin Ibn Rahman, Ashani Wickramarachchi, Naresh Parajuli, Saurav Khatiwada, Deep Dutta","doi":"10.17925/EE.2024.20.2.8","DOIUrl":"10.17925/EE.2024.20.2.8","url":null,"abstract":"<p><p><b>Background.</b> Obeticholic acid (OCA) has emerged as a promising drug in the management of nonalcoholic fatty liver disease (NAFLD). This meta-analysis aimed to analyse the therapeutic effect of OCA on NAFLD. <b>Methods.</b> Randomized controlled trials (RCTs) involving patients with NAFLD receiving OCA in the intervention arm and placebo in the control arm were searched throughout the electronic databases. The primary outcomes were changes in non-invasive markers of hepatic fibrosis and liver histology. The secondary outcomes included changes in liver enzymes, metabolic parameters from baseline and adverse events (AEs). <b>Results.</b> Four RCTs involving 1,278 subjects met the inclusion criteria. Over 6 weeks to 18 months of clinical use, OCA outperformed placebo in resolving definite nonalcoholic steatohepatitis (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.04-2.48], p=0.03) and improving fibrosis (OR 2.23, 95% CI [1.56-3.20], p<0.0001), hepatocellular ballooning (OR 1.83, 95% CI [1.35-2.47], p<0.0001) and lobular inflammation (OR 1.62, 95% CI [1.13-2.32], p=0.009). OCA did not improve the enhanced liver fibrosis score and steatosis better than placebo, and demonstrated superior efficacy compared with the placebo in reducing serum alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase levels. Although a favourable effect of OCA over placebo was seen in body-weight reduction, the OCA use was associated with adverse changes in lipid parameters. Except for the greater risk of pruritus and constipation, the AE profile was comparable between the OCA and placebo groups. <b>Conclusions.</b> OCA has a favourable efficacy in improving liver histology and liver enzymes. However, the worsening of lipid parameters and other AEs with the OCA use warrants further investigation.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 2","pages":"54-61"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-10-15DOI: 10.17925/EE.2024.20.2.13
Nicholas A Householder, Coby Ray
Background: Long-duration thyroid eye disease (TED) may present with persistent proptosis despite the absence of inflammatory symptoms, and treatment options have been limited to surgical intervention. Recently, teprotumumab, a monoclonal antibody, has garnered interest as a non-surgical option to reduce proptosis in such cases. This systematic review investigates the impact of teprotumumab on reducing proptosis in long-duration TED. Methods: A search was conducted across major online databases, and data were aggregated from observational studies, clinical trials and case series. Nine studies met the inclusion criteria. Cumulative and weighted effect measures were synthesized. The biases and limitations of each study were assessed. Results: Existing evidence shows teprotumumab to be highly efficacious in reducing proptosis in chronic TED; however, there are significant limitations in the quality of existing evidence. The cumulative meta-analysis reveals a mean proptosis reduction of 3.05 ± 0.54 mm across 182 orbits from nine studies, and the weighted meta-analysis shows a mean reduction of 2.69 ± 0.53 mm across 172 orbits from eight studies. Discussion: While existing clinical studies are open to bias and intrinsically limited, the meta-analysis dilutes the risk of bias by weighting more precise evidence, providing the highest quality evidence to date. Further research is essential to understand teprotumumab's long-term efficacy and comparative advantages over surgical options. These findings have significant implications for treating persistent proptosis in patients with long-duration TED, potentially offering a non-surgical alternative where options were previously limited.
{"title":"Teprotumumab's Impact on Proptosis in Long-duration Thyroid Eye Disease: A Systematic Review and Meta-analysis.","authors":"Nicholas A Householder, Coby Ray","doi":"10.17925/EE.2024.20.2.13","DOIUrl":"https://doi.org/10.17925/EE.2024.20.2.13","url":null,"abstract":"<p><p><b>Background:</b> Long-duration thyroid eye disease (TED) may present with persistent proptosis despite the absence of inflammatory symptoms, and treatment options have been limited to surgical intervention. Recently, teprotumumab, a monoclonal antibody, has garnered interest as a non-surgical option to reduce proptosis in such cases. This systematic review investigates the impact of teprotumumab on reducing proptosis in long-duration TED. <b>Methods:</b> A search was conducted across major online databases, and data were aggregated from observational studies, clinical trials and case series. Nine studies met the inclusion criteria. Cumulative and weighted effect measures were synthesized. The biases and limitations of each study were assessed. <b>Results:</b> Existing evidence shows teprotumumab to be highly efficacious in reducing proptosis in chronic TED; however, there are significant limitations in the quality of existing evidence. The cumulative meta-analysis reveals a mean proptosis reduction of 3.05 ± 0.54 mm across 182 orbits from nine studies, and the weighted meta-analysis shows a mean reduction of 2.69 ± 0.53 mm across 172 orbits from eight studies. <b>Discussion:</b> While existing clinical studies are open to bias and intrinsically limited, the meta-analysis dilutes the risk of bias by weighting more precise evidence, providing the highest quality evidence to date. Further research is essential to understand teprotumumab's long-term efficacy and comparative advantages over surgical options. These findings have significant implications for treating persistent proptosis in patients with long-duration TED, potentially offering a non-surgical alternative where options were previously limited.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 2","pages":"100-109"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-03-28DOI: 10.17925/EE.2024.20.2.4
Rodolfo A Rey
The term "DSD" was coined for "disorders of sex development", referring to conditions where the chromosomal, gonadal and/or genital sex is discordant or ambiguous, to replace terms considered imprecise and stigmatizing. Recently, the term "disorder" has been questioned and the term "differences" has been proposed as not stigmatizing, reflecting that the term DSD should be depathologized. In this opinion article, I discuss the importance of using precise technical terminologies amongst healthcare professionals, in the era of "precision medicine", to avoid misleading diagnoses or classifications while being extremely careful to use sensitive terminologies when interacting with patients and their families. On the other hand, I challenge the concept that DSD are not disorders.
{"title":"The Approach to Patients with Disorders of Sex Development (DSD) in the Era of Precision Medicine: The Careful Use of Terminology.","authors":"Rodolfo A Rey","doi":"10.17925/EE.2024.20.2.4","DOIUrl":"https://doi.org/10.17925/EE.2024.20.2.4","url":null,"abstract":"<p><p>The term \"DSD\" was coined for \"disorders of sex development\", referring to conditions where the chromosomal, gonadal and/or genital sex is discordant or ambiguous, to replace terms considered imprecise and stigmatizing. Recently, the term \"disorder\" has been questioned and the term \"differences\" has been proposed as not stigmatizing, reflecting that the term DSD should be depathologized. In this opinion article, I discuss the importance of using precise technical terminologies amongst healthcare professionals, in the era of \"precision medicine\", to avoid misleading diagnoses or classifications while being extremely careful to use sensitive terminologies when interacting with patients and their families. On the other hand, I challenge the concept that DSD are not disorders.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 2","pages":"16-18"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dry eye disease (DED) is an inadequately addressed condition in the diabetes management process and can significantly impact the quality of life and self-care. Therefore, it was imperative to review DED in the diabetic population. The aim of this article was to obtain insights into the correlation between dry eye and diabetes, with a focus on data published in the Indian population. A comprehensive literature review was performed using MEDLINE and Google Scholar, along with an internet-based search of publicly available information and peer-reviewed publications that may not have been indexed in these databases. The recommendations from several important societies for patients with DED have also been reviewed. Major aspects commonly associated with DED and diabetes have been addressed, and specific suggestions for screening, diagnosis and treatment have been described. Therefore, this review could be an invaluable resource for doctors managing patients with both conditions.
干眼症(DED)是糖尿病治疗过程中一个未得到充分解决的问题,会严重影响患者的生活质量和自我护理。因此,对糖尿病人群中的干眼症进行研究势在必行。本文旨在深入了解干眼症与糖尿病之间的相关性,重点关注在印度人群中发表的数据。我们使用 MEDLINE 和 Google Scholar 进行了全面的文献综述,同时还在互联网上搜索了可能未被这些数据库收录的公开信息和同行评审出版物。此外,还查阅了几个重要学会对 DED 患者的建议。其中讨论了与 DED 和糖尿病相关的主要方面,并介绍了有关筛查、诊断和治疗的具体建议。因此,这篇综述对于管理这两种疾病患者的医生来说是非常宝贵的资源。
{"title":"Dry Eye in Diabetes: The Indian Diabetic and Endocrine Eye Diseases (INDEED) Review.","authors":"Sanjay Kalra, Nikhil Sharad Gokhale, Ganapathi Bantwal, Roopashri Matada, Shehla Shaikh, Varsha Pawar, Maneesha Khalse, Kamlesh Patel","doi":"10.17925/EE.2024.20.2.6","DOIUrl":"10.17925/EE.2024.20.2.6","url":null,"abstract":"<p><p>Dry eye disease (DED) is an inadequately addressed condition in the diabetes management process and can significantly impact the quality of life and self-care. Therefore, it was imperative to review DED in the diabetic population. The aim of this article was to obtain insights into the correlation between dry eye and diabetes, with a focus on data published in the Indian population. A comprehensive literature review was performed using MEDLINE and Google Scholar, along with an internet-based search of publicly available information and peer-reviewed publications that may not have been indexed in these databases. The recommendations from several important societies for patients with DED have also been reviewed. Major aspects commonly associated with DED and diabetes have been addressed, and specific suggestions for screening, diagnosis and treatment have been described. Therefore, this review could be an invaluable resource for doctors managing patients with both conditions.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 2","pages":"30-41"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-06-06DOI: 10.17925/EE.2024.20.2.10
Deep Dutta, A B M Kamrul-Hasan, Lakshmi Nagendra, Saptarshi Bhattacharya
Aims: To date, no meta-analysis has analyzed the efficacy and safety of tirzepatide as an anti-obesity medication in individuals without diabetes. This meta-analysis was undertaken to address this knowledge gap. Materials and methods: Electronic databases were searched for randomized controlled trials (RCTs) involving individuals with obesity without diabetes receiving tirzepatide in the intervention arm and placebo in the control arm. The primary outcome was the percentage change in weight from baseline, and the secondary outcomes included the change in weight from baseline; a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25%; glycaemic parameters; lipid parameters and adverse events. Results: From 281 initially screened articles, data from 2 RCTs involving 1,852 participants were analyzed. The efficacy and safety of tirzepatide 15 mg (or the highest tolerable dose) versus placebo were analyzed. The percentage change in body weight was higher with tirzepatide than with placebo (mean difference [MD]: -19.44%; 95% confidence interval [CI]: -22.48 to -16.41; p<0.00001). Tirzepatide also had a higher absolute reduction in body weight (MD: -17.55 kg; 95% CI: -32.15 to -2.95; p<0.00001). Higher percentages of people on tirzepatide had a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% compared with placebo. Improvements in glycaemic and cardiometabolic parameters were observed with tirzepatide. Tirzepatide was associated with a higher number of participants with one or more adverse events, which leads to treatment discontinuation, and severe or serious gastrointestinal events. Conclusion: This meta-analysis provides exciting data on the impressive weight loss properties of tirzepatide over 72 weeks of clinical use in individuals with obesity without diabetes.
{"title":"Efficacy and Safety of Novel Twincretin Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, as an Anti-obesity Medicine in Individuals Without Diabetes: A Systematic Review and Meta-analysis.","authors":"Deep Dutta, A B M Kamrul-Hasan, Lakshmi Nagendra, Saptarshi Bhattacharya","doi":"10.17925/EE.2024.20.2.10","DOIUrl":"10.17925/EE.2024.20.2.10","url":null,"abstract":"<p><p><b>Aims:</b> To date, no meta-analysis has analyzed the efficacy and safety of tirzepatide as an anti-obesity medication in individuals without diabetes. This meta-analysis was undertaken to address this knowledge gap. <b>Materials and methods:</b> Electronic databases were searched for randomized controlled trials (RCTs) involving individuals with obesity without diabetes receiving tirzepatide in the intervention arm and placebo in the control arm. The primary outcome was the percentage change in weight from baseline, and the secondary outcomes included the change in weight from baseline; a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25%; glycaemic parameters; lipid parameters and adverse events. <b>Results:</b> From 281 initially screened articles, data from 2 RCTs involving 1,852 participants were analyzed. The efficacy and safety of tirzepatide 15 mg (or the highest tolerable dose) versus placebo were analyzed. The percentage change in body weight was higher with tirzepatide than with placebo (mean difference [MD]: -19.44%; 95% confidence interval [CI]: -22.48 to -16.41; p<0.00001). Tirzepatide also had a higher absolute reduction in body weight (MD: -17.55 kg; 95% CI: -32.15 to -2.95; p<0.00001). Higher percentages of people on tirzepatide had a weight reduction of ≥5%, ≥10%, ≥15%, ≥20% and ≥25% compared with placebo. Improvements in glycaemic and cardiometabolic parameters were observed with tirzepatide. Tirzepatide was associated with a higher number of participants with one or more adverse events, which leads to treatment discontinuation, and severe or serious gastrointestinal events. <b>Conclusion:</b> This meta-analysis provides exciting data on the impressive weight loss properties of tirzepatide over 72 weeks of clinical use in individuals with obesity without diabetes.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 2","pages":"72-80"},"PeriodicalIF":0.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11548363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-11-08DOI: 10.17925/EE.2023.20.1.4
Eleni Armeni, Ashley Grossman
Previous studies have suggested that corticotroph tumours are associated with the overexpression of cyclin E and that the inactivation of cyclin-dependent kinases, which activate cyclin E, may have antisecretory and antiproliferative effects. Seliciclib, also known as R-roscovitine, is a pituitary-targeting agent shown to inhibit the growth of corticotroph tumour cells via cyclin E and retinoblastoma protein-mediated pathways. A recent study investigated the role of seliciclib in regulating biochemical parameters in a small number of patients with Cushing's disease, providing preliminary data on its possible therapeutic effectiveness in treating this disorder.
以往的研究表明,皮质营养肿瘤与细胞周期蛋白 E 的过度表达有关,而激活细胞周期蛋白 E 的细胞周期蛋白依赖性激酶失活可能具有抗分泌和抗增殖作用。Seliciclib 又称 R-roscovitine,是一种垂体靶向药物,可通过细胞周期蛋白 E 和视网膜母细胞瘤蛋白介导的途径抑制肾上腺皮质肿瘤细胞的生长。最近的一项研究调查了赛力昔单抗在调节少数库欣病患者生化指标方面的作用,为其在治疗这种疾病方面可能的疗效提供了初步数据。
{"title":"Seliciclib: A New Treatment for Cushing's Disease?","authors":"Eleni Armeni, Ashley Grossman","doi":"10.17925/EE.2023.20.1.4","DOIUrl":"10.17925/EE.2023.20.1.4","url":null,"abstract":"<p><p>Previous studies have suggested that corticotroph tumours are associated with the overexpression of cyclin E and that the inactivation of cyclin-dependent kinases, which activate cyclin E, may have antisecretory and antiproliferative effects. Seliciclib, also known as R-roscovitine, is a pituitary-targeting agent shown to inhibit the growth of corticotroph tumour cells via cyclin E and retinoblastoma protein-mediated pathways. A recent study investigated the role of seliciclib in regulating biochemical parameters in a small number of patients with Cushing's disease, providing preliminary data on its possible therapeutic effectiveness in treating this disorder.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 1","pages":"3-4"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-11-09DOI: 10.17925/EE.2023.20.1.2
Evana Valenzuela-Scheker, David N Bimston, Hubert Golingan, Allan Golding, R Mack Harrell
Background: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). Methods: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. Results: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper-and mixed echogenicity (solid atypical mixed echogenicity nodules-SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-l ike nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40-70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. Conclusion: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10-20%).
背景:目的:确定具有2015年美国甲状腺协会超声风险分层系统(NC ATA)无法分类的声像图模式的实性非典型混合回声甲状腺结节(SAMENs)的患病率和恶性风险(ROM)。研究方法我们搜索了前瞻性收集的内分泌手术甲状腺结节(TN)数据库,尤其关注那些属于 NC ATA 的实性结节。根据 2015 年美国甲状腺协会超声风险分层系统(ATA USRSS),一种算法将每个结节划分为五个 ATA 风险组之一。算法无法分配到风险组的 TN 被视为 NC ATA,随后进行分析。此外,我们还使用基于 2017 年美国放射学会甲状腺成像报告和数据系统(ACR-TIRADS)的算法对该组进行了分类。我们特别关注导致 2015 ATA USRSS 未分类的特征以及该组患者的细针穿刺活检 (FNAB) 细胞学和手术病理学结果。结果:我们评估了 5040 个结节的数据,其中 1772 个进行了手术病理检查。有150个实性结节未按2015 ATA USRSS分类,所有这些结节都表现出非典型特征,同时伴有等、异、高和混合回声(实性非典型混合回声结节-SAMENs)。其中 60 个结节被切除并送去做手术病理检查,90 个结节则没有做手术切除。在未进行手术的 90 个结节中,82 个进行了 FNAB 和细胞学评估。在我们的150例SAMEN中,40例经手术组织学检查为恶性,6例经细胞学检查可能为恶性(不伴有乳头状类核特征的非侵袭性滤泡性甲状腺肿瘤的SAMEN ROM总数占31%)。在我们的SAMEN组中,最常见的声像图模式是等回声实性成分伴微钙化(占所有切除恶性结节的28/40-70%)。在我们切除的恶性 SAMEN 中,50% 表现为滤泡型肿瘤结构,48% 表现为乳头状结构。结论我们的研究表明,SAMENs至少有一个可疑的声像图特征:包括(1)微钙化;(2)边缘不规则或其他可疑特征;opulation,且ROM(31%)高于2015 ATA USRSS的中危组(10-20%)。
{"title":"Challenges in Risk Stratification of Solid Atypical Mixed Echogenicity Thyroid Nodules.","authors":"Evana Valenzuela-Scheker, David N Bimston, Hubert Golingan, Allan Golding, R Mack Harrell","doi":"10.17925/EE.2023.20.1.2","DOIUrl":"10.17925/EE.2023.20.1.2","url":null,"abstract":"<p><p><b>Background</b>: To determine the prevalence and risk of malignancy (ROM) in solid atypical mixed echogenicity thyroid nodules (SAMENs) with sonographic patterns not classifiable by the 2015 American Thyroid Association Ultrasound Risk Stratification System (NC ATA). <b>Methods</b>: We searched our prospectively collected endocrine surgery thyroid nodule (TN) database, with particular attention to those solid nodules that were NC ATA. An algorithm assigned each into one of the five ATA risk groups per the 2015 American Thyroid Association Ultrasound Risk Stratification System (ATA USRSS). TNs that the algorithm could not assign to a risk group were deemed NC ATA and were subsequently analyzed. Additionally, we categorized this group using an algorithm based on the 2017 American College of Radiology Thyroid Imaging Reporting and Data System (ACR-TIRADS). We were specifically interested in the characteristics that resulted in non-classification by the 2015 ATA USRSS and the fine needle aspiration biopsy (FNAB) cytology and surgical pathology results from the group. <b>Results</b>: We evaluated data from 5,040 nodules, of which 1,772 had surgical pathology. There were 150 solid nodules not classified by 2015 ATA USRSS, all of which demonstrated atypical features along with iso-, hetero-, hyper-and mixed echogenicity (solid atypical mixed echogenicity nodules-SAMENs). Sixty of these nodules were excised and sent for surgical pathology, while 90 were followed without surgical excision. Out of the 90 that did not undergo surgery, 82 underwent FNAB with cytologic evaluation. Of our 150 SAMENs, 40 were malignant by surgical histology and six were likely malignant by cytology (total SAMEN ROM without noninvasive follicular thyroid neoplasm with papillary-l ike nuclear features 31%). The most common sonographic pattern present in our SAMEN group consisted of an isoechoic solid component with microcalcifications (28/40-70% of all excised malignant nodules). In our excised malignant SAMENs, 50% demonstrated follicular-patterned neoplastic architecture while 48% displayed papillary architecture. <b>Conclusion</b>: Our study demonstrates that SAMENs with at least one suspicious sonographic feature: including (1) microcalcifications; (2) irregular or other suspicious margins,;opulation, and a higher ROM (31%) than the intermediate-risk group of the 2015 ATA USRSS (10-20%).</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 1","pages":"58-62"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2024-01-22DOI: 10.17925/EE.2024.20.1.9
Meliha Melin Uygur, Marta Villanova, Stefano Frara, Andrea Giustina
The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide.
{"title":"Clinical Pharmacology of Oral Octreotide Capsules for the Treatment of Acromegaly.","authors":"Meliha Melin Uygur, Marta Villanova, Stefano Frara, Andrea Giustina","doi":"10.17925/EE.2024.20.1.9","DOIUrl":"10.17925/EE.2024.20.1.9","url":null,"abstract":"<p><p>The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 1","pages":"37-42"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-01Epub Date: 2023-11-08DOI: 10.17925/EE.2023.20.1.3
David S McLaren, Khyatisha Seejore, Julie Lynch, Robert D Murray
Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 µg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 - 2.5 x upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.
{"title":"Oral Octreotide Capsules and Paltusotine in Management of Acromegaly.","authors":"David S McLaren, Khyatisha Seejore, Julie Lynch, Robert D Murray","doi":"10.17925/EE.2023.20.1.3","DOIUrl":"10.17925/EE.2023.20.1.3","url":null,"abstract":"<p><p>Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 µg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 - 2.5 x upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.</p>","PeriodicalId":75231,"journal":{"name":"TouchREVIEWS in endocrinology","volume":"20 1","pages":"32-36"},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11132651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}