Pub Date : 2026-02-03DOI: 10.1016/j.eprac.2026.01.751
Xi Xiong, Chun Ho Wong, Kimberly H Tsoi, Connie H N Loong, Carol H Y Fong, Alan C H Lee, Chi Ho Lee, Kathryn C B Tan, Yu Cho Woo, Manju Chandran, David T W Lui
Objective: We described treatment approaches after 20 doses of denosumab, including continuation or transition to zoledronic acid or romosozumab, and examined subsequent BMD trajectories.
Methods: This retrospective single-centre cohort included patients who received ≥20 consecutive doses of denosumab at the Osteoporosis Centre between June 2012 and December 2024. Characteristics of patients who continued denosumab were compared with those who transitioned to zoledronic acid or romosozumab. BMD was obtained from DXA, and trajectory analyses were restricted to patients without delayed dosing and with BMD reassessment after the 20th dose.
Results: Fifty-four patients received ≥20 doses (mean age 72.9 years, 98.1% female). The 20th-dose BMD T-score was the major determinant of subsequent treatment: 2 patients with the lowest T-scores transitioned to romosozumab, 4 with the highest transitioned to zoledronic acid, and 48 continued denosumab. Continuing denosumab led to further BMD gains at the lumbar spine and femoral neck but not the total hip. Transition to zoledronic acid led to partial loss of the year-10 BMD gains. Transition to romosozumab led to further BMD gain at the lumbar spine only. No cases of atypical femoral fracture or osteonecrosis of the jaw were reported.
Conclusion: After ≥20 doses of denosumab, most patients continued treatment, guided largely by the 20th-dose BMD T-score. Continuing denosumab beyond 10 years resulted in further increases in BMD at the lumbar spine and maintenance of BMD at the femoral neck, whereas transition to zoledronic acid led to partial loss of previous gains and transition to romosozumab increased lumbar spine BMD only.
{"title":"Denosumab Therapy Beyond 10 Years: Subsequent Treatment and Densitometric Outcomes.","authors":"Xi Xiong, Chun Ho Wong, Kimberly H Tsoi, Connie H N Loong, Carol H Y Fong, Alan C H Lee, Chi Ho Lee, Kathryn C B Tan, Yu Cho Woo, Manju Chandran, David T W Lui","doi":"10.1016/j.eprac.2026.01.751","DOIUrl":"10.1016/j.eprac.2026.01.751","url":null,"abstract":"<p><strong>Objective: </strong>We described treatment approaches after 20 doses of denosumab, including continuation or transition to zoledronic acid or romosozumab, and examined subsequent BMD trajectories.</p><p><strong>Methods: </strong>This retrospective single-centre cohort included patients who received ≥20 consecutive doses of denosumab at the Osteoporosis Centre between June 2012 and December 2024. Characteristics of patients who continued denosumab were compared with those who transitioned to zoledronic acid or romosozumab. BMD was obtained from DXA, and trajectory analyses were restricted to patients without delayed dosing and with BMD reassessment after the 20th dose.</p><p><strong>Results: </strong>Fifty-four patients received ≥20 doses (mean age 72.9 years, 98.1% female). The 20th-dose BMD T-score was the major determinant of subsequent treatment: 2 patients with the lowest T-scores transitioned to romosozumab, 4 with the highest transitioned to zoledronic acid, and 48 continued denosumab. Continuing denosumab led to further BMD gains at the lumbar spine and femoral neck but not the total hip. Transition to zoledronic acid led to partial loss of the year-10 BMD gains. Transition to romosozumab led to further BMD gain at the lumbar spine only. No cases of atypical femoral fracture or osteonecrosis of the jaw were reported.</p><p><strong>Conclusion: </strong>After ≥20 doses of denosumab, most patients continued treatment, guided largely by the 20th-dose BMD T-score. Continuing denosumab beyond 10 years resulted in further increases in BMD at the lumbar spine and maintenance of BMD at the femoral neck, whereas transition to zoledronic acid led to partial loss of previous gains and transition to romosozumab increased lumbar spine BMD only.</p>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124142","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}
Pub Date : 2026-02-03DOI: 10.1016/j.eprac.2026.01.750
Sarah Azad, Srisai A Turangi, Anery Patel, Abbey Fingeret, Ana Yuil-Valdes, Johnson Thomas, Anupam Kotwal
Objectives: For indeterminate thyroid nodules, molecular tests offer high negative predictive value (NPV), reducing missed malignancies, but have limited positive predictive value (PPV), potentially leading to unnecessary surgeries. We evaluated how integrating artificial intelligence-based imaging (AIBx V2) with ThyroSeq v3 could enhance diagnostic accuracy.
Methods: We retrospectively analyzed 108 indeterminate thyroid nodules. Surgical pathology was available for 42 nodules for primary analysis; the remaining 66, without surgical pathology, were deemed benign for analytic purposes and included in the total cohort for secondary analysis reflecting real-world practice. We calculated test performance for AIBx V2 alone, ThyroSeq v3 alone, and a combined approach (AIBx V2+Mol). In the combined approach, when ThyroSeq v3 reported "Malignant", but the estimated malignancy probability was intermediate or lower, the final classification deferred to AIBx V2.
Results: In the surgical pathology subset (n = 42), ThyroSeq v3 demonstrated high sensitivity (0.95) but moderate specificity (0.45), leading to a PPV of 0.65. AIBx V2 improved specificity (0.60) but had lower sensitivity (0.77). The AIBx V2+Mol approach retained high sensitivity (0.95) while raising specificity to 0.60, improving PPV to 0.72 and AUC from 0.70 to 0.77. In the entire cohort (n = 108), AIBx V2+Mol maintained excellent sensitivity (0.95) and further enhanced specificity, 0.90 vs0.87, PPV 0.72 vs0.65, and AUC 0.93 vs0.91.
Conclusions: Integrating AIBx V2 imaging model with ThyroSeq v3 preserved the high sensitivity of molecular testing while improving specificity and PPV. These exploratory results need validation in larger studies before the combined model is incorporated into clinical practice.
目的：对于不确定的甲状腺结节，分子检测提供了高阴性预测值（NPV），减少了恶性肿瘤的漏诊，但阳性预测值（PPV）有限，可能导致不必要的手术。我们评估了如何将基于人工智能的成像（AIBx V2）与ThyroSeq v3相结合来提高诊断准确性。方法：回顾性分析108例不确定甲状腺结节。对42例结节进行手术病理初步分析；其余66例，无手术病理，为分析目的被认为是良性的，并纳入总队列进行二次分析，反映现实世界的实践。我们计算了单独使用AIBx V2、单独使用ThyroSeq v3和联合使用（AIBx V2+Mol）的测试性能。在联合方法中，当ThyroSeq v3报告为“恶性”，但估计的恶性概率为中等或更低时，最终的分类推迟到AIBx V2。结果：在外科病理亚组（n=42）中，ThyroSeq v3表现出高敏感性（0.95）和中等特异性（0.45），PPV为0.65。AIBx V2提高了特异性（0.60），但降低了敏感性（0.77）。AIBx V2+Mol方法保持了较高的灵敏度（0.95），特异性提高到0.60，PPV提高到0.72，AUC从0.70提高到0.77。在整个队列（n=108）中，AIBx V2+Mol保持了良好的敏感性（0.95），并进一步增强了特异性（0.90 vs 0.87, PPV 0.72 vs 0.65, AUC 0.93 vs 0.91）。结论：将AIBx V2成像模型与ThyroSeq v3结合，在保持分子检测的高灵敏度的同时，提高了特异性和PPV。这些探索性的结果需要在更大规模的研究中验证，然后才能将联合模型纳入临床实践。
{"title":"Improving Diagnostic Precision in Thyroid Pathology by Synergistic Use of AI and Molecular Markers.","authors":"Sarah Azad, Srisai A Turangi, Anery Patel, Abbey Fingeret, Ana Yuil-Valdes, Johnson Thomas, Anupam Kotwal","doi":"10.1016/j.eprac.2026.01.750","DOIUrl":"10.1016/j.eprac.2026.01.750","url":null,"abstract":"<p><strong>Objectives: </strong>For indeterminate thyroid nodules, molecular tests offer high negative predictive value (NPV), reducing missed malignancies, but have limited positive predictive value (PPV), potentially leading to unnecessary surgeries. We evaluated how integrating artificial intelligence-based imaging (AIBx V2) with ThyroSeq v3 could enhance diagnostic accuracy.</p><p><strong>Methods: </strong>We retrospectively analyzed 108 indeterminate thyroid nodules. Surgical pathology was available for 42 nodules for primary analysis; the remaining 66, without surgical pathology, were deemed benign for analytic purposes and included in the total cohort for secondary analysis reflecting real-world practice. We calculated test performance for AIBx V2 alone, ThyroSeq v3 alone, and a combined approach (AIBx V2+Mol). In the combined approach, when ThyroSeq v3 reported \"Malignant\", but the estimated malignancy probability was intermediate or lower, the final classification deferred to AIBx V2.</p><p><strong>Results: </strong>In the surgical pathology subset (n = 42), ThyroSeq v3 demonstrated high sensitivity (0.95) but moderate specificity (0.45), leading to a PPV of 0.65. AIBx V2 improved specificity (0.60) but had lower sensitivity (0.77). The AIBx V2+Mol approach retained high sensitivity (0.95) while raising specificity to 0.60, improving PPV to 0.72 and AUC from 0.70 to 0.77. In the entire cohort (n = 108), AIBx V2+Mol maintained excellent sensitivity (0.95) and further enhanced specificity, 0.90 vs0.87, PPV 0.72 vs0.65, and AUC 0.93 vs0.91.</p><p><strong>Conclusions: </strong>Integrating AIBx V2 imaging model with ThyroSeq v3 preserved the high sensitivity of molecular testing while improving specificity and PPV. These exploratory results need validation in larger studies before the combined model is incorporated into clinical practice.</p>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124139","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}
Pub Date : 2026-02-02DOI: 10.1016/j.eprac.2026.01.012
Rozalina G McCoy, Kavya Sindu Swarna, Eric C Polley, Yihong Deng, Sagar Chawla, Joshua J Neumiller, Rodolfo J Galindo, Guillermo E Umpierrez, Joseph S Ross, Mindy M Mickelson, Jeph Herrin
Objective: Lower extremity complications significantly impact morbidity and health care costs among people with type 2 diabetes (T2D). Evidence regarding the impact of different glucose-lowering medications on these outcomes remains inconclusive.
Methods: We emulated a target trial using 2 linked national claims databases (Optum Labs Data Warehouse, Medicare fee-for-service). We included adults with T2D at moderate cardiovascular risk who initiated glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), or sulfonylurea between 2014 and 2021, and used propensity score inverse probability of treatment weighted Cox proportional hazards models to compare the incidence rates of the primary composite outcome of incident foot ulcer/abscess, osteomyelitis, Charcot arthropathy, or amputation across the 4 medication classes under the intention-to-treat framework.
Results: The weighted study cohort included 81,998 DPP-4i initiators, 43,734 GLP-1RA initiators, 57,399 SGLT2i initiators, and 206,374 sulfonylurea initiators; they were well balanced on all examined baseline characteristics. Sulfonylurea use was associated with a higher risk of the composite lower extremity complications outcome compared with DPP-4i (hazard ratio [HR] 1.15; 95% CI 1.11-1.19), GLP-1RA (HR 1.20; 95% CI 1.13-1.28), and SGLT2i (HR 1.08; 95% CI 1.02-1.14). SGLT2i use was also associated with a higher risk compared with GLP-1RA (HR 1.11; 95% CI 1.03-1.21). Amputation events were rare in all treatment groups.
Conclusion: We observed greater relative risks of lower extremity complications with sulfonylurea use compared with DPP-4i, GLP-1RA, and SGLT2i use, and with SGLT2i use compared with GLP-1RA use. Reassuringly, the absolute event rate differences between the medication classes were <1%. Diabetes management teams may consider these medication-associated risks when selecting glucose-lowering therapies for individuals without high cardiovascular risk, especially those predisposed to lower extremity morbidity.
{"title":"Lower Extremity Complications in Adults With Type 2 Diabetes Treated With Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas: An Emulated Target Trial.","authors":"Rozalina G McCoy, Kavya Sindu Swarna, Eric C Polley, Yihong Deng, Sagar Chawla, Joshua J Neumiller, Rodolfo J Galindo, Guillermo E Umpierrez, Joseph S Ross, Mindy M Mickelson, Jeph Herrin","doi":"10.1016/j.eprac.2026.01.012","DOIUrl":"10.1016/j.eprac.2026.01.012","url":null,"abstract":"<p><strong>Objective: </strong>Lower extremity complications significantly impact morbidity and health care costs among people with type 2 diabetes (T2D). Evidence regarding the impact of different glucose-lowering medications on these outcomes remains inconclusive.</p><p><strong>Methods: </strong>We emulated a target trial using 2 linked national claims databases (Optum Labs Data Warehouse, Medicare fee-for-service). We included adults with T2D at moderate cardiovascular risk who initiated glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), or sulfonylurea between 2014 and 2021, and used propensity score inverse probability of treatment weighted Cox proportional hazards models to compare the incidence rates of the primary composite outcome of incident foot ulcer/abscess, osteomyelitis, Charcot arthropathy, or amputation across the 4 medication classes under the intention-to-treat framework.</p><p><strong>Results: </strong>The weighted study cohort included 81,998 DPP-4i initiators, 43,734 GLP-1RA initiators, 57,399 SGLT2i initiators, and 206,374 sulfonylurea initiators; they were well balanced on all examined baseline characteristics. Sulfonylurea use was associated with a higher risk of the composite lower extremity complications outcome compared with DPP-4i (hazard ratio [HR] 1.15; 95% CI 1.11-1.19), GLP-1RA (HR 1.20; 95% CI 1.13-1.28), and SGLT2i (HR 1.08; 95% CI 1.02-1.14). SGLT2i use was also associated with a higher risk compared with GLP-1RA (HR 1.11; 95% CI 1.03-1.21). Amputation events were rare in all treatment groups.</p><p><strong>Conclusion: </strong>We observed greater relative risks of lower extremity complications with sulfonylurea use compared with DPP-4i, GLP-1RA, and SGLT2i use, and with SGLT2i use compared with GLP-1RA use. Reassuringly, the absolute event rate differences between the medication classes were <1%. Diabetes management teams may consider these medication-associated risks when selecting glucose-lowering therapies for individuals without high cardiovascular risk, especially those predisposed to lower extremity morbidity.</p>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118068","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}
Pub Date : 2026-02-01Epub Date: 2025-10-01DOI: 10.1016/j.eprac.2025.09.205
Michael Ndaa MSc , Prashant K. Pandya DO, FAASLD , Jordan Swensson MD , Niharika Samala MD , Saima Ajaz BSc, MBBS, MPhil, PhD, Dip, IBLM/BSLM , Deepak Joshi PhD, FRCP , Walid S. Ayoub MD, FAASLD, AGAF , Fatih Akisik MD
Introduction
As treatments for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) emerge, patient eligibility assessment and monitoring is increasingly important. To assess the reliability of noninvasive imaging technologies in MASLD, we systematically reviewed the literature for studies on technical repeatability.
Methods
PubMed Central and MEDLINE were searched (2015-2025) for studies in MASLD that examined the repeatability of: magnetic resonance-derived iron-corrected T1 (cT1), liver fat content (LFC), and magnetic resonance elastography (MRE); ultrasound-based vibration controlled transient elastography liver stiffness measurement (VCTE LSM), controlled attenuation parameter and shear wave elastography. The relative repeatability coefficient (%RC) for same-day or different-day (%RCDD) repeat tests were summarized, and available data pooled using random-effects-meta-analysis.
Results
Our search identified 19 studies including 1040 individuals (mean age 45 years; 43% female). The pooled random-effects average %RCDD was 7% for cT1, 12% for LFC, 22% for MRE, 73% for VCTE LSM, and 26% for controlled attenuation parameter, with a median interval of 14 days between repeat scans. Relative repeated measures on the same day values were consistently lower across all tests. In the context of MASLD monitoring, the %RCDD for MRE and VCTE LSM overlapped with previously reported thresholds for clinically-meaningful change for treatment responders (15% and 30%, respectively). In contrast, the %RCs for cT1 and LFC were below established thresholds for clinically-meaningful change (9% and 30%, respectively).
Conclusion
This systematic review and meta-analysis showed that cT1 and LFC are more reliable in detecting change in liver health in people living with MASLD-metabolic dysfunction-associated steatohepatitis, compared to liver stiffness. Liver stiffness measurements are less suited to monitoring individual patients.
{"title":"Reliable Monitoring of Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease Using Imaging: A Systematic Literature Review and Meta-Analysis on Measurement Repeatability","authors":"Michael Ndaa MSc , Prashant K. Pandya DO, FAASLD , Jordan Swensson MD , Niharika Samala MD , Saima Ajaz BSc, MBBS, MPhil, PhD, Dip, IBLM/BSLM , Deepak Joshi PhD, FRCP , Walid S. Ayoub MD, FAASLD, AGAF , Fatih Akisik MD","doi":"10.1016/j.eprac.2025.09.205","DOIUrl":"10.1016/j.eprac.2025.09.205","url":null,"abstract":"<div><h3>Introduction</h3><div>As treatments for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) emerge, patient eligibility assessment and monitoring is increasingly important. To assess the reliability of noninvasive imaging technologies in MASLD, we systematically reviewed the literature for studies on technical repeatability.</div></div><div><h3>Methods</h3><div>PubMed Central and MEDLINE were searched (2015-2025) for studies in MASLD that examined the repeatability of: magnetic resonance-derived iron-corrected T1 (cT1), liver fat content (LFC), and magnetic resonance elastography (MRE); ultrasound-based vibration controlled transient elastography liver stiffness measurement (VCTE LSM), controlled attenuation parameter and shear wave elastography. The relative repeatability coefficient (%RC) for same-day or different-day (%RC<sub>DD</sub>) repeat tests were summarized, and available data pooled using random-effects-meta-analysis.</div></div><div><h3>Results</h3><div>Our search identified 19 studies including 1040 individuals (mean age 45 years; 43% female). The pooled random-effects average %RC<sub>DD</sub> was 7% for cT1, 12% for LFC, 22% for MRE, 73% for VCTE LSM, and 26% for controlled attenuation parameter, with a median interval of 14 days between repeat scans. Relative repeated measures on the same day values were consistently lower across all tests. In the context of MASLD monitoring, the %RC<sub>DD</sub> for MRE and VCTE LSM overlapped with previously reported thresholds for clinically-meaningful change for treatment responders (15% and 30%, respectively). In contrast, the %RCs for cT1 and LFC were below established thresholds for clinically-meaningful change (9% and 30%, respectively).</div></div><div><h3>Conclusion</h3><div>This systematic review and meta-analysis showed that cT1 and LFC are more reliable in detecting change in liver health in people living with MASLD-metabolic dysfunction-associated steatohepatitis, compared to liver stiffness. Liver stiffness measurements are less suited to monitoring individual patients.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 258-267"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225181","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}
Differentiated thyroid cancers (DTCs), including papillary, follicular, and oncocytic subtypes, are generally associated with an excellent prognosis due to their responsiveness to conventional therapies, including surgery, thyroid-stimulating hormone suppression, and radioactive iodine (RAI) therapy. However, a subset of patients develops RAI-refractory disease, characterized by tumor dedifferentiation and loss of iodine avidity, resulting in disease progression despite standard interventions. This group poses a considerable therapeutic challenge and is associated with markedly poorer outcomes. This review summarizes contemporary approaches to advanced RAI-refractory DTC.
Methods
This review consolidates the current evidence for diagnosing, evaluating, and managing advanced RAI-refractory DTC.
Results
Recent advancements have transformed the treatment landscape with the emergence of systemic therapies such as antiangiogenic multikinase inhibitors and genotype-directed therapies that offer improved disease control in advanced settings. It explores the pathophysiological basis of refractoriness, prognostic implications, treatment selection strategies—including active surveillance, locoregional therapies, redifferentiation approaches, and systemic therapies—and outlines practical considerations for clinicians.
Conclusion
Future directions including immunotherapy, novel agents, and personalized therapy strategies are also discussed. Emphasis is placed on precision oncology, toxicity management, and the role of multidisciplinary care in optimizing patient outcomes.
分化型甲状腺癌（DTC），包括乳头状、滤泡和嗜瘤细胞亚型，由于其对常规治疗的反应性，包括手术、促甲状腺激素（TSH）抑制和放射性碘（RAI）治疗，通常具有良好的预后。然而，一小部分患者发展为放射性碘难治性（RAI-R）疾病，其特征是肿瘤去分化和碘亲和力丧失，尽管有标准干预，但仍导致疾病进展。这一组具有相当大的治疗挑战，并且与明显较差的结果相关。随着抗血管生成多激酶抑制剂（aaMKIs）和基因型导向疗法等系统性疗法的出现，最近的进展已经改变了治疗领域，这些疗法可以改善晚期疾病的控制。本文综述了目前诊断、评估和治疗晚期rar - r DTC的证据。它探讨了难治性的病理生理学基础、预后影响、治疗选择策略——包括积极监测、局部区域治疗、再分化方法和全身治疗——并概述了临床医生的实际考虑。未来的发展方向包括免疫治疗、新型药物和个性化治疗策略。重点放在精确肿瘤学、毒性管理和多学科护理在优化患者结果中的作用。
{"title":"Approach and Challenges for Patients With Advanced Radioiodine-Refractory Differentiated Thyroid Cancer","authors":"Dipen C. Patel MD , Irina Azaryan MD , Bhavana Konda MD, MPH","doi":"10.1016/j.eprac.2025.09.203","DOIUrl":"10.1016/j.eprac.2025.09.203","url":null,"abstract":"<div><h3>Objective</h3><div>Differentiated thyroid cancers (DTCs), including papillary, follicular, and oncocytic subtypes, are generally associated with an excellent prognosis due to their responsiveness to conventional therapies, including surgery, thyroid-stimulating hormone suppression, and radioactive iodine (RAI) therapy. However, a subset of patients develops RAI-refractory disease, characterized by tumor dedifferentiation and loss of iodine avidity, resulting in disease progression despite standard interventions. This group poses a considerable therapeutic challenge and is associated with markedly poorer outcomes. This review summarizes contemporary approaches to advanced RAI-refractory DTC.</div></div><div><h3>Methods</h3><div>This review consolidates the current evidence for diagnosing, evaluating, and managing advanced RAI-refractory DTC.</div></div><div><h3>Results</h3><div>Recent advancements have transformed the treatment landscape with the emergence of systemic therapies such as antiangiogenic multikinase inhibitors and genotype-directed therapies that offer improved disease control in advanced settings. It explores the pathophysiological basis of refractoriness, prognostic implications, treatment selection strategies—including active surveillance, locoregional therapies, redifferentiation approaches, and systemic therapies—and outlines practical considerations for clinicians.</div></div><div><h3>Conclusion</h3><div>Future directions including immunotherapy, novel agents, and personalized therapy strategies are also discussed. Emphasis is placed on precision oncology, toxicity management, and the role of multidisciplinary care in optimizing patient outcomes.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 268-279"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212068","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}
Pub Date : 2026-02-01Epub Date: 2025-10-14DOI: 10.1016/j.eprac.2025.10.006
Betina Biagetti MD , Pedro Marques MD , Roser Ferrer MD , Luís Miguel Cardoso MD , Eva Venegas Moreno MD , Carmen Fajardo-Montañana MD , Laura Gonzalez-Fernandez MD , Marta María Pérez Pena MD , Rogelio García-Centeno MD , Claudia Lozano-Aida MD , Iría Novoa-Testa MD , Eider Pascual-Corrales MD , Raúl Sánchón MD , Fernando Guerrero-Pérez MD , Rosario Oliva Rodríguez MD , Beatriz Rodríguez Jiménez MD , María Dolores Ollero García MD , Ana Irigaray Echarri MD , Andreu Simó-Servat MD , María Dolores Moure Rodríguez MD , Marta Araujo-Castro MD
Objective
To identify distinct clinical phenotypes in acromegaly based on growth hormone (GH) assay standardization and unsupervised machine learning.
Methods
This was a multicenter cross-sectional analysis of 416 patients diagnosed with acromegaly from 2010 onward. Patients were stratified according to baseline serum GH levels standardized to the assay-specific upper limit of normal (GHxULN) using a binary classification (GH-B: <1.0×ULN vs ≥1.0×ULN) and a four-tier classification (GH-4: <0.25, 0.25-0.99, 1.0-9.9, ≥10×ULN). Unsupervised cluster analysis included age, GHxULN, insulin-like growth factor 1 (IGF-1)xULN, tumor diameter, and T2-weighted signal intensity.
Results
Overall, 36% of patients had GH levels within the normal reference range for their assay (GH-B <1.0×ULN). Microadenomas (23.1%) were more frequent in older patients and associated with lower GH/IGF-1 levels. Across GH-4 categories, significant gradients were observed for age (z = −5.34, P < .001), tumor size (z = 8.01, P < .001), IGF-1 (z = 9.00, P < .001), and symptom duration (z = 4.34, P < .001). Higher GH categories were associated with greater odds of arthropathy (odds ratio 3.5, P = .015 for 1.0-9.9×ULN and odds ratio 6.58, P = .002 for ≥10×ULN). Cluster analysis revealed 3 phenotypes: cluster 1 (49.0%) [older age, lower GH/IGF-1, intermediate tumor size]; cluster 2 (44.4%) [intermediate age, moderate biochemical activity, smaller tumors]; cluster 3 (6.6%) [younger age, markedly elevated GH/IGF-1, large aggressive tumors].
Conclusion
GH standardization to assay-specific ULN reveals clinically meaningful phenotypes in acromegaly that correlate with age, tumor characteristics, and disease severity (particularly arthropathy). GHxULN complements IGF-1 by capturing tumor secretory activity, and this stratification approach may support more individualized clinical decision-making.
{"title":"Growth Hormone Assay-Adjusted Standardization Reveals Distinct Clinical Phenotypes in Acromegaly","authors":"Betina Biagetti MD , Pedro Marques MD , Roser Ferrer MD , Luís Miguel Cardoso MD , Eva Venegas Moreno MD , Carmen Fajardo-Montañana MD , Laura Gonzalez-Fernandez MD , Marta María Pérez Pena MD , Rogelio García-Centeno MD , Claudia Lozano-Aida MD , Iría Novoa-Testa MD , Eider Pascual-Corrales MD , Raúl Sánchón MD , Fernando Guerrero-Pérez MD , Rosario Oliva Rodríguez MD , Beatriz Rodríguez Jiménez MD , María Dolores Ollero García MD , Ana Irigaray Echarri MD , Andreu Simó-Servat MD , María Dolores Moure Rodríguez MD , Marta Araujo-Castro MD","doi":"10.1016/j.eprac.2025.10.006","DOIUrl":"10.1016/j.eprac.2025.10.006","url":null,"abstract":"<div><h3>Objective</h3><div>To identify distinct clinical phenotypes in acromegaly based on growth hormone (GH) assay standardization and unsupervised machine learning.</div></div><div><h3>Methods</h3><div>This was a multicenter cross-sectional analysis of 416 patients diagnosed with acromegaly from 2010 onward. Patients were stratified according to baseline serum GH levels standardized to the assay-specific upper limit of normal (GHxULN) using a binary classification (GH-B: <1.0×ULN vs ≥1.0×ULN) and a four-tier classification (GH-4: <0.25, 0.25-0.99, 1.0-9.9, ≥10×ULN). Unsupervised cluster analysis included age, GHxULN, insulin-like growth factor 1 (IGF-1)xULN, tumor diameter, and T2-weighted signal intensity.</div></div><div><h3>Results</h3><div>Overall, 36% of patients had GH levels within the normal reference range for their assay (GH-B <1.0×ULN). Microadenomas (23.1%) were more frequent in older patients and associated with lower GH/IGF-1 levels. Across GH-4 categories, significant gradients were observed for age (z = −5.34, <em>P</em> < .001), tumor size (z = 8.01, <em>P</em> < .001), IGF-1 (z = 9.00, <em>P</em> < .001), and symptom duration (z = 4.34, <em>P</em> < .001). Higher GH categories were associated with greater odds of arthropathy (odds ratio 3.5, <em>P</em> = .015 for 1.0-9.9×ULN and odds ratio 6.58, <em>P</em> = .002 for ≥10×ULN). Cluster analysis revealed 3 phenotypes: cluster 1 (49.0%) [older age, lower GH/IGF-1, intermediate tumor size]; cluster 2 (44.4%) [intermediate age, moderate biochemical activity, smaller tumors]; cluster 3 (6.6%) [younger age, markedly elevated GH/IGF-1, large aggressive tumors].</div></div><div><h3>Conclusion</h3><div>GH standardization to assay-specific ULN reveals clinically meaningful phenotypes in acromegaly that correlate with age, tumor characteristics, and disease severity (particularly arthropathy). GHxULN complements IGF-1 by capturing tumor secretory activity, and this stratification approach may support more individualized clinical decision-making.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 236-245"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307314","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}
Pub Date : 2026-02-01Epub Date: 2025-09-30DOI: 10.1016/j.eprac.2025.09.202
Jie Liu MD , Yanying Li MD , Jifang Liu MD , Zhang Ye MD , He Liu MD , Xiaofeng Chai MD , Huijuan Zhu MD , Bing Xing MD , Wei Lian MD , Xiaolan Lian MD , Naishi Li MD , Lin Lu MD , Mei Zhang MD , Lian Duan MD, PhD , Yong Yao MD , Kan Deng MD
Objective
Hyperthyroidism can harm bone health, though it is seldom reported in thyroid-stimulating hormone/thyrotropin (TSH)-secreting adenomas (TSHomas). This study assessed bone mineral density (BMD) and bone turnover markers (BTMs) in TSHoma patients versus euthyroid controls and evaluated the impact of surgical treatment on bone metabolism.
Methods
We retrospectively reviewed 85 TSHoma patients who underwent BMD tests. Of these, 71 had baseline BMD data and were matched with 71 euthyroid healthy controls by age, sex, and body mass index. BMD and BTMs were measured.
Results
TSHoma patients demonstrated significantly reduced BMD compared to matched euthyroid controls across all skeletal sites, with reductions of 12.4% at the lumbar spine (1.06 ± 0.19 vs 1.21 ± 0.14 g/cm2, P < .001), 8.5% at the femoral neck (0.86 ± 0.14 vs 0.94 ± 0.11 g/cm2, P < .001), and 14.8% at the total hip (0.86 ± 0.13 vs 1.01 ± 0.12 g/cm2, P < .001). Baseline BTMs revealed elevated osteoblastic (procollagen type 1 N-terminal propeptide 108 [60, 202] ng/mL) and osteoclastic markers (β-CTX 0.84 [0.62, 1.30] ng/mL). Besides, free triiodothyronine showed strong positive correlations with BTMs: alkaline phosphatase (r = 0.45, P = .005), β-CTX (r = 0.61, P < .001), and procollagen type 1 N-terminal propeptide (r = 0.73, P = .004). Following tumor resection, BTMs decreased significantly: alkaline phosphatase (91 [74.25, 119.5] to 71 [68, 94] U/L, P = .003) and β-CTX (0.75 [0.57, 0.94] to 0.22 [0.21, 0.45] ng/mL, P = .008). Postoperative BMD revealed stabilization with nonsignificant improvements at all measured skeletal sites.
Conclusion
TSHoma patients exhibit significant BMD deficits compared to euthyroid controls. Surgery effectively reduces BTMs while stabilizing BMD, preventing further deterioration rather than restoring bone density.
目的：甲状腺机能亢进对骨健康有危害，但在tshoma中很少报道。本研究评估了TSHoma患者与正常甲状腺对照者的骨密度（BMD）和骨转换标志物（BTM），并评估了手术治疗对骨代谢的影响。方法：我们回顾性分析了85例接受BMD检查的TSHoma患者。其中，71人有基线BMD数据，并与71名甲状腺功能正常的健康对照者按年龄、性别和BMI进行匹配。测量BMD和btm。结果：与匹配的甲状腺正常对照组相比，TSHoma患者在所有骨骼部位的骨密度均显著降低，腰椎降低12.4%(1.06±0.19比1.21±0.14 g/cm2, p < 0.001)，股骨颈降低8.5%(0.86±0.14比0.94±0.11 g/cm2, p < 0.001)，全髋关节降低14.8%（0.86±0.13比1.01±0.12 g/cm2, p < 0.001）。基线BTMs显示成骨细胞[P1NP 108 (60,202) ng/mL]和破骨细胞标志物[β-CTX 0.84 (0.62, 1.30) ng/mL]升高。FT3与BTMs呈显著正相关：ALP （r = 0.45, p = 0.005）、β-CTX （r = 0.61, p < 0.001）、P1NP （r = 0.73, p = 0.004）。肿瘤切除后，BTMs显著降低：ALP[91（74.25, 119.5）至71 (68,94)U/L, p = 0.003], β-CTX[0.75（0.57, 0.94）至0.22 (0.21,0.45)ng/mL, p = 0.008]。术后骨密度显示稳定，所有测量的骨骼部位均无明显改善。结论：与甲状腺功能正常的对照组相比，TSHoma患者表现出明显的BMD缺陷。手术有效地减少脑转移，同时稳定骨密度，防止进一步恶化，而不是恢复骨密度。
{"title":"Impairment of Bone Mineral Density in Pituitary Thyrotropin-Secreting Adenomas: A Retrospective, Controlled Study","authors":"Jie Liu MD , Yanying Li MD , Jifang Liu MD , Zhang Ye MD , He Liu MD , Xiaofeng Chai MD , Huijuan Zhu MD , Bing Xing MD , Wei Lian MD , Xiaolan Lian MD , Naishi Li MD , Lin Lu MD , Mei Zhang MD , Lian Duan MD, PhD , Yong Yao MD , Kan Deng MD","doi":"10.1016/j.eprac.2025.09.202","DOIUrl":"10.1016/j.eprac.2025.09.202","url":null,"abstract":"<div><h3>Objective</h3><div>Hyperthyroidism can harm bone health, though it is seldom reported in thyroid-stimulating hormone/thyrotropin (TSH)-secreting adenomas (TSHomas). This study assessed bone mineral density (BMD) and bone turnover markers (BTMs) in TSHoma patients versus euthyroid controls and evaluated the impact of surgical treatment on bone metabolism.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 85 TSHoma patients who underwent BMD tests. Of these, 71 had baseline BMD data and were matched with 71 euthyroid healthy controls by age, sex, and body mass index. BMD and BTMs were measured.</div></div><div><h3>Results</h3><div>TSHoma patients demonstrated significantly reduced BMD compared to matched euthyroid controls across all skeletal sites, with reductions of 12.4% at the lumbar spine (1.06 ± 0.19 vs 1.21 ± 0.14 g/cm<sup>2</sup>, <em>P</em> < .001), 8.5% at the femoral neck (0.86 ± 0.14 vs 0.94 ± 0.11 g/cm<sup>2</sup>, <em>P</em> < .001), and 14.8% at the total hip (0.86 ± 0.13 vs 1.01 ± 0.12 g/cm<sup>2</sup>, <em>P</em> < .001). Baseline BTMs revealed elevated osteoblastic (procollagen type 1 N-terminal propeptide 108 [60, 202] ng/mL) and osteoclastic markers (β-CTX 0.84 [0.62, 1.30] ng/mL). Besides, free triiodothyronine showed strong positive correlations with BTMs: alkaline phosphatase (<em>r</em> = 0.45, <em>P</em> = .005), β-CTX (<em>r</em> = 0.61, <em>P</em> < .001), and procollagen type 1 N-terminal propeptide (<em>r</em> = 0.73, <em>P</em> = .004). Following tumor resection, BTMs decreased significantly: alkaline phosphatase (91 [74.25, 119.5] to 71 [68, 94] U/L, <em>P</em> = .003) and β-CTX (0.75 [0.57, 0.94] to 0.22 [0.21, 0.45] ng/mL, <em>P</em> = .008). Postoperative BMD revealed stabilization with nonsignificant improvements at all measured skeletal sites.</div></div><div><h3>Conclusion</h3><div>TSHoma patients exhibit significant BMD deficits compared to euthyroid controls. Surgery effectively reduces BTMs while stabilizing BMD, preventing further deterioration rather than restoring bone density.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 172-178"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212113","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}
Pub Date : 2026-02-01Epub Date: 2025-09-30DOI: 10.1016/j.eprac.2025.09.201
Alberto Piasentier MD , Maria Francesca Birtolo MD , Bianca Turci MD , Walter Vena MD , Alessandro Fanti MD , Emanuela Morenghi MD , Lucrezia MS. Gentile MD , Luca Balzarini MD , Antonio C. Bossi MD , Alfredo Berruti MD , Giovanni Lughezzani MD , Ciro Franzese MD , Fabio De Vincenzo MD , Marta Scorsetti MD , Paolo A. Zucali MD , Andrea G. Lania MD, PhD , Gherardo Mazziotti MD, PhD
Objective
This prospective study investigated the real-world effectiveness of bisphosphonates and denosumab in reducing vertebral fracture (VF) risk induced by androgen deprivation therapies (ADTs).
Methods
Two hundred twenty-six consecutive men (mean age 74.8 ± 6.9 years) undergoing ADT were evaluated for morphometric VFs at baseline and after 26.1 ± 10.7 months of follow-up (range 18-64). Following enrollment, 153 patients commenced bisphosphonates (98 cases) or denosumab (55 cases), while 73 patients (32.3%) received only vitamin D and calcium supplementation. As an additional control group, we enrolled 62 consecutive men (mean age 74.9 ± 7.2 years) under chronic ADTs who had been neither evaluated nor treated for skeletal fragility before study entry.
Results
Incident VFs were found in 16 of 226 (7.1%) patients enrolled in the prospective study and in 18 of 62 (29.0%) control subjects (P < .001). The risk of VFs was significantly lower in patients treated with bone-active drugs as compared to those treated with vitamin D (hazard ratio 0.26, 95% CI 0.09-0.73; P = .01), without significant difference between denosumab and bisphosphonate treatment (P = .423), although denosumab-treated patients had lower bone mineral density, higher serum C-terminal telopeptide of type I collagen values, and more prevalent VFs. Noteworthy, incident VFs were significantly lower in patients receiving vitamin D with calcium as compared to those subjects under chronic ADT who had never been evaluated and treated for skeletal fragility prior to the study (12.3% vs 29.0%; P = .016).
Conclusion
In real-world clinical practice, bisphosphonates or denosumab might be effective in reducing the risk of VFs related to ADTs.
{"title":"Effectiveness of Bisphosphonates and Denosumab on Risk of Vertebral Fractures in Prostate Cancer Patients Under Androgen Deprivation Therapies: A Real-World Prospective Study","authors":"Alberto Piasentier MD , Maria Francesca Birtolo MD , Bianca Turci MD , Walter Vena MD , Alessandro Fanti MD , Emanuela Morenghi MD , Lucrezia MS. Gentile MD , Luca Balzarini MD , Antonio C. Bossi MD , Alfredo Berruti MD , Giovanni Lughezzani MD , Ciro Franzese MD , Fabio De Vincenzo MD , Marta Scorsetti MD , Paolo A. Zucali MD , Andrea G. Lania MD, PhD , Gherardo Mazziotti MD, PhD","doi":"10.1016/j.eprac.2025.09.201","DOIUrl":"10.1016/j.eprac.2025.09.201","url":null,"abstract":"<div><h3>Objective</h3><div>This prospective study investigated the real-world effectiveness of bisphosphonates and denosumab in reducing vertebral fracture (VF) risk induced by androgen deprivation therapies (ADTs).</div></div><div><h3>Methods</h3><div>Two hundred twenty-six consecutive men (mean age 74.8 ± 6.9 years) undergoing ADT were evaluated for morphometric VFs at baseline and after 26.1 ± 10.7 months of follow-up (range 18-64). Following enrollment, 153 patients commenced bisphosphonates (98 cases) or denosumab (55 cases), while 73 patients (32.3%) received only vitamin D and calcium supplementation. As an additional control group, we enrolled 62 consecutive men (mean age 74.9 ± 7.2 years) under chronic ADTs who had been neither evaluated nor treated for skeletal fragility before study entry.</div></div><div><h3>Results</h3><div>Incident VFs were found in 16 of 226 (7.1%) patients enrolled in the prospective study and in 18 of 62 (29.0%) control subjects (<em>P</em> < .001). The risk of VFs was significantly lower in patients treated with bone-active drugs as compared to those treated with vitamin D (hazard ratio 0.26, 95% CI 0.09-0.73; <em>P</em> = .01), without significant difference between denosumab and bisphosphonate treatment (<em>P</em> = .423), although denosumab-treated patients had lower bone mineral density, higher serum C-terminal telopeptide of type I collagen values, and more prevalent VFs. Noteworthy, incident VFs were significantly lower in patients receiving vitamin D with calcium as compared to those subjects under chronic ADT who had never been evaluated and treated for skeletal fragility prior to the study (12.3% vs 29.0%; <em>P</em> = .016).</div></div><div><h3>Conclusion</h3><div>In real-world clinical practice, bisphosphonates or denosumab might be effective in reducing the risk of VFs related to ADTs.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 164-171"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212123","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}
Pub Date : 2026-02-01Epub Date: 2025-10-01DOI: 10.1016/j.eprac.2025.09.204
Hussam Alkaissi MD, MS , Sara Talvacchio RN , Alberta Derkyi CRNP , Sriram Gubbi MD , Alberto Pappo MD , Catherine M. Gordon MD, MS , John Glod MD, PhD , Zhengping Zhuang MD, PhD , Karel Pacak MD, PhD, DSc
Objectives
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors of the adrenal medulla and autonomic ganglia, respectively. Germline and somatic genetic drivers are identified in up to 70% of cases. Hypoxia-inducible factor 2α (HIF-2α), encoded by the EPAS1 (HIF2A) gene, plays a central role in PPGL pathogenesis and can be stabilized directly or indirectly by pathogenic variants of several genes, collectively called pseudohypoxia cluster (or Cluster 1). Belzutifan, a small-molecule HIF-2α inhibitor, has demonstrated efficacy in von Hippel–Lindau-related cancers, renal cell carcinoma, and few case reports of PPGL. We report real-world outcomes of belzutifan therapy in 5 patients with recurrent, multifocal, or metastatic EPAS1 (HIF2A)-related PPGL.
Methods
Clinical parameters, biochemical markers, tumor burden (RECIST 1.1), and treatment-related adverse events were carefully monitored, and recorded.
Results
Four of 5 patients (80%) achieved a partial response, and one patient had stable disease, with no disease progression to date. The average reduction in the sum of tumor diameters was 36.8%. Chromogranin A, erythropoietin, and hemoglobin declined by 69%, 97%, and 13%, respectively, eliminating the need for therapeutic phlebotomy in patients with prior erythrocytosis. Catecholamine normalization allowed discontinuation or reduction of antihypertensive medications in 2 patients. Adverse events included hypoxia and anemia (1/5), mild transaminase elevation (2/5), and fatigue with weight gain (1/5).
Conclusions
Belzutifan is a highly effective and well-tolerated therapeutic option for EPAS1(HIF2A)-related PPGL, producing substantial biochemical and radiographic responses, improved blood pressure control, and resolution of erythrocytosis. These findings support belzutifan as a promising genotype-driven therapy for pseudohypoxia-driven PPGL.
{"title":"Belzutifan for HIF2A-Related Pheochromocytoma and Paraganglioma: A Retrospective Study of Real-World Data","authors":"Hussam Alkaissi MD, MS , Sara Talvacchio RN , Alberta Derkyi CRNP , Sriram Gubbi MD , Alberto Pappo MD , Catherine M. Gordon MD, MS , John Glod MD, PhD , Zhengping Zhuang MD, PhD , Karel Pacak MD, PhD, DSc","doi":"10.1016/j.eprac.2025.09.204","DOIUrl":"10.1016/j.eprac.2025.09.204","url":null,"abstract":"<div><h3>Objectives</h3><div>Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors of the adrenal medulla and autonomic ganglia, respectively. Germline and somatic genetic drivers are identified in up to 70% of cases. Hypoxia-inducible factor 2α (HIF-2α), encoded by the <em>EPAS1</em> (<em>HIF2A</em>) gene, plays a central role in PPGL pathogenesis and can be stabilized directly or indirectly by pathogenic variants of several genes, collectively called pseudohypoxia cluster (or Cluster 1). Belzutifan, a small-molecule HIF-2α inhibitor, has demonstrated efficacy in von Hippel–Lindau-related cancers, renal cell carcinoma, and few case reports of PPGL. We report real-world outcomes of belzutifan therapy in 5 patients with recurrent, multifocal, or metastatic <em>EPAS1</em> (<em>HIF2A</em>)-related PPGL.</div></div><div><h3>Methods</h3><div>Clinical parameters, biochemical markers, tumor burden (RECIST 1.1), and treatment-related adverse events were carefully monitored, and recorded.</div></div><div><h3>Results</h3><div>Four of 5 patients (80%) achieved a partial response, and one patient had stable disease, with no disease progression to date. The average reduction in the sum of tumor diameters was 36.8%. Chromogranin A, erythropoietin, and hemoglobin declined by 69%, 97%, and 13%, respectively, eliminating the need for therapeutic phlebotomy in patients with prior erythrocytosis. Catecholamine normalization allowed discontinuation or reduction of antihypertensive medications in 2 patients. Adverse events included hypoxia and anemia (1/5), mild transaminase elevation (2/5), and fatigue with weight gain (1/5).</div></div><div><h3>Conclusions</h3><div>Belzutifan is a highly effective and well-tolerated therapeutic option for <em>EPAS1</em>(<em>HIF2A</em>)-related PPGL, producing substantial biochemical and radiographic responses, improved blood pressure control, and resolution of erythrocytosis. These findings support belzutifan as a promising genotype-driven therapy for pseudohypoxia-driven PPGL.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 201-205"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225248","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}
Pub Date : 2026-02-01Epub Date: 2025-10-28DOI: 10.1016/j.eprac.2025.10.015
Elaine Young AB , Andrew R. Goyette AB , Jeremy F. Alkire AB , Nour L. Khachemoune AB , Natalie Bellini DNP, BC-ADM, CDCES , Diana Isaacs PharmD, BCPS, BCACP, CDCES, BC-ADM, FADCES, FCCP
Objective
To review the clinical evidence for automated insulin delivery (AID) use during pregnancy in people with pregestational diabetes, provide an overview of AID systems available in the United States, and offer practical tips and considerations for clinicians working with pregnant patients on these systems.
Methods
We synthesized findings from all randomized controlled trials investigating AID use in people with pregestational diabetes. We also compared the features of 6 AID systems and shared clinical insights on how their settings can be adjusted to better meet pregnancy-specific glycemic targets.
Results
Six randomized controlled trials were included, all in type 1 diabetes. Some demonstrated better glycemic outcomes in patients using AID compared to sensor-augmented pump therapy or standard insulin therapy. Others found no significant differences. Maternal and neonatal outcomes were similar to standard care, though some studies found that AID users had reduced gestational weight gain among other improvements. CamAPS FX is the only food and Drug Administration-cleared AID system for use in type 1 diabetes pregnancy, though it is not yet available in the United States. While no AID system has demonstrated the ability to meet all pregnancy-specific glycemic targets, some systems are more customizable making it easier to achieve the tighter glycemic targets in pregnancy.
Conclusion
For pregnant women using AID systems, there are strategies and workarounds to aid in achieving pregnancy-specific glycemic targets. However, no system consistently meets all targets. More research is needed to understand how AID use during pregnancy impacts maternal and fetal outcomes and patient-reported outcomes, especially for pre-existing type 2 diabetes.
{"title":"A Review of Automated Insulin Delivery Use in Type 1 Diabetes During Pregnancy","authors":"Elaine Young AB , Andrew R. Goyette AB , Jeremy F. Alkire AB , Nour L. Khachemoune AB , Natalie Bellini DNP, BC-ADM, CDCES , Diana Isaacs PharmD, BCPS, BCACP, CDCES, BC-ADM, FADCES, FCCP","doi":"10.1016/j.eprac.2025.10.015","DOIUrl":"10.1016/j.eprac.2025.10.015","url":null,"abstract":"<div><h3>Objective</h3><div>To review the clinical evidence for automated insulin delivery (AID) use during pregnancy in people with pregestational diabetes, provide an overview of AID systems available in the United States, and offer practical tips and considerations for clinicians working with pregnant patients on these systems.</div></div><div><h3>Methods</h3><div>We synthesized findings from all randomized controlled trials investigating AID use in people with pregestational diabetes. We also compared the features of 6 AID systems and shared clinical insights on how their settings can be adjusted to better meet pregnancy-specific glycemic targets.</div></div><div><h3>Results</h3><div>Six randomized controlled trials were included, all in type 1 diabetes. Some demonstrated better glycemic outcomes in patients using AID compared to sensor-augmented pump therapy or standard insulin therapy. Others found no significant differences. Maternal and neonatal outcomes were similar to standard care, though some studies found that AID users had reduced gestational weight gain among other improvements. CamAPS FX is the only food and Drug Administration-cleared AID system for use in type 1 diabetes pregnancy, though it is not yet available in the United States. While no AID system has demonstrated the ability to meet all pregnancy-specific glycemic targets, some systems are more customizable making it easier to achieve the tighter glycemic targets in pregnancy.</div></div><div><h3>Conclusion</h3><div>For pregnant women using AID systems, there are strategies and workarounds to aid in achieving pregnancy-specific glycemic targets. However, no system consistently meets all targets. More research is needed to understand how AID use during pregnancy impacts maternal and fetal outcomes and patient-reported outcomes, especially for pre-existing type 2 diabetes.</div></div>","PeriodicalId":11682,"journal":{"name":"Endocrine Practice","volume":"32 2","pages":"Pages 286-292"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145408480","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号