Ichiro Yamauchi Japan

Dr. Ichiro Yamauchi is an Assistant Professor in the Department of Diabetes, Endocrinology and Nutrition at Kyoto University Graduate School of Medicine, Japan. He is a physician-scientist whose research focuses on thyroid physiology, integrating basic, translational, and clinical research approaches. His work has primarily explored the regulation of thyroid hormone action and the mechanisms of thyroid hormone secretion, using transcriptomic analyses and multi-organ evaluation systems for thyroid hormone signaling in mouse models. In addition to thyroid physiology, Dr. Yamauchi has contributed to research on endocrine disorders, including immune checkpoint inhibitor–related endocrine adverse events, genetic metabolic diseases, and endocrine therapeutics. His work has been recognized with several honors, including the Research Award from the Japan Endocrine Society and the Shichijo Prize from the Japan Thyroid Association. He plays active roles in the Japan Endocrine Society, particularly in clinical education, and serves as a director of the Japan Thyroid Association and as a coordinator of the NexT-JTA project, promoting collaboration among the next generation of thyroid researchers.

20 MARCH

Time	Session

13:50 15:20	[Symposium] Thyroid (2) Thyroid Eye Disease Management Shyang-Rong ShihTaiwan Moderator The impact of mutational status on the heterogeneity of MEN1Multiple Endocrine Neoplasia type 1 (MEN1) is a rare syndromic disease primarily characterized by parathyroid adenomas, duodenopancreatic neuroendocrine neoplasms (dpNENs), and pituitary neuroendocrine tumors (pitNETs). Although over 750 germline MEN1 mutations have been identified, there is no definitive genotype-phenotype correlation, and specific mutations cannot reliably predict clinical presentations. However, the overall presence or absence of a germline mutation fundamentally alters the disease trajectory. This presentation investigates the clinical heterogeneity between germline mutation-positive (GP-MEN1) and mutation-negative (GN-MEN1) patients. Approximately 10-30% of patients meeting clinical MEN1 criteria are GN-MEN1, which may represent phenocopies (e.g., MEN4, MEN5) or sporadic co-occurrences. Distinct clinical disparities exist between the two cohorts. GP-MEN1 patients exhibit an earlier median onset (33-35 years), aggressive and multiglandular disease, and a high probability of developing a third cardinal tumor, leading to a poorer prognosis. Conversely, GN-MEN1 patients present significantly later (46-52 years), rarely develop a third cardinal tumor, and experience a more indolent course with a life expectancy comparable to the general population. In a cohort analysis from National Taiwan University Hospital (NTUH), the paradigm of pitNETs in MEN1 has shifted towards non-functioning microadenomas due to modern screening. GP-MEN1 patients with pitNETs were diagnosed at a younger age, showed higher sellar floor involvement, and had a higher prevalence of adrenal tumors and non-functioning GEP-NENs. In contrast, GN-MEN1 patients were older and more frequently presented with insulinomas. In conclusion, germline mutational status is a critical determinant of MEN1 clinical heterogeneity. Genetic testing is essential not only for confirming diagnoses and facilitating targeted therapies but also for exonerating non-carriers. Although current guidelines recommend uniform surveillance for all MEN1 diagnostic categories, the distinctively indolent phenotype of GN-MEN1 suggests that a modified, de-escalated surveillance approach may be more appropriate and warrants further formal investigation. Yueh-Ju TsaiTaiwan Moderator Novel Biomarkers and Treatment Strategies in Thyroid Eye Disease Chia-Hung LinTaiwan Speaker Novel Biomarkers and Treatment Strategies in Thyroid Eye DiseaseThyroid Eye Disease (TED), also known as Graves' orbitopathy, remains a complex autoimmune condition that significantly impacts patients' vision and quality of life. Traditionally, management has relied mainly on non-specific anti-inflammatory therapies. However, as our understanding of its molecular pathogenesis evolves, there is an increasing clinical demand for more precise diagnostic tools and targeted therapeutic interventions. This presentation provides a comprehensive overview of the current landscape and future directions in the management of TED. We will discuss the emergence of novel serum and molecular biomarkers that offer potential for earlier diagnosis and more accurate prediction of disease progression. These biomarkers may bridge the gap between clinical observation and underlying immunological activity. Furthermore, we will explore the shift in treatment paradigms, moving from conventional systemic corticosteroids toward innovative biological agents. By targeting specific signaling pathways involved in orbital inflammation and remodeling, these new strategies aim to provide more effective and durable clinical outcomes. The integration of novel biomarkers and advanced treatment modalities is reshaping the management of TED. Moving toward a more individualized approach will allow clinicians to optimize therapeutic timing and selection, ultimately improving the long-term prognosis for patients with this challenging condition. Management of Thyroid Eye Disease: Insights from Clinical Experience and MRI Findings in Japan Ichiro YamauchiJapan Speaker Management of Thyroid Eye Disease: Insights from Clinical Experience and MRI Findings in JapanIn Japan, disease activity of thyroid eye disease (TED) is commonly assessed using magnetic resonance imaging (MRI) in addition to clinical activity score (CAS). Recently, we proposed an MRI-guided categorization of active moderate-to-severe TED based on our retrospective data. We retrospectively analyzed TED cases treated at our department between 2015 and 2022 with a combination of daily steroid pulse therapy and orbital radiation. Among 44 cases with diplopia, we classified 17 cases as severe (diplopia in the primary position) and 27 as non-severe (diplopia only in non-primary positions). The severe group was older (median 67 years) and had lower TSAb titers (median 324%) compared to the non-severe group (median 56 years, median TSAb 2443%). CAS was similar between the groups. MRI revealed that proptosis was more pronounced in the non-severe group (median 21.4 mm) than in the severe group (median 17.5 mm), whereas the difference in proptosis between eyes was larger in the severe group (median 2.0 mm) than in the non-severe group (median 0.9 mm). High signal intensity of orbital fat on STIR sequence was more frequently observed in the non-severe group (68.2%) than in the severe group (20.0%). These findings suggest that TED patients with severe diplopia are characterized by older age, lower TSAb titers, and greater asymmetry in proptosis. In contrast, CAS and STIR signal intensity of orbital fat were not indicative of severity. In this context, severe diplopia often develops despite low CAS and mild proptosis. We also present our clinical experience with teprotumumab, an anti–IGF-1 receptor antibody. Since its launch in Japan in 2024, we have treated several patients with severe TED, the majority of whom showed remarkable improvement in clinical features. However, adverse effects such as hearing impairment and hyperglycemia were occasionally observed, highlighting the importance of appropriate management. In conclusion, MRI-guided evaluation provides valuable insights for individualized management of TED. Evidence regarding the efficacy of teprotumumab remains limited in the subtype characterized by severe diplopia, which often presents with low CAS and mild proptosis. The MRI-guided approach may help clinicians select optimal therapeutic strategies, including steroid pulse therapy, teprotumumab, and other emerging agents. Update on Thyroid Eye Disease Management - Asia Pacific Perspectives Kelvin ChongHong Kong, China Speaker Update on Thyroid Eye Disease Management - Asia Pacific PerspectivesExisting guidelines/recommendations/consensus on the management of thyroid eye disease (TED)/Graves' orbitopathy (GO) pose significant difficulties when applied in the Asia Pacific region. The presenter will share his experiences and challenges in setting up the first thyroid eye clinic in Hong Kong, developing an image-guided medical and surgical decompression, while looking into the future of intelligence-based management of TED/GO. 101

Time

Session

13:50

15:20

[Symposium] Thyroid (2)

Thyroid Eye Disease Management

Shyang-Rong ShihTaiwan Moderator The impact of mutational status on the heterogeneity of MEN1Multiple Endocrine Neoplasia type 1 (MEN1) is a rare syndromic disease primarily characterized by parathyroid adenomas, duodenopancreatic neuroendocrine neoplasms (dpNENs), and pituitary neuroendocrine tumors (pitNETs). Although over 750 germline MEN1 mutations have been identified, there is no definitive genotype-phenotype correlation, and specific mutations cannot reliably predict clinical presentations. However, the overall presence or absence of a germline mutation fundamentally alters the disease trajectory. This presentation investigates the clinical heterogeneity between germline mutation-positive (GP-MEN1) and mutation-negative (GN-MEN1) patients. Approximately 10-30% of patients meeting clinical MEN1 criteria are GN-MEN1, which may represent phenocopies (e.g., MEN4, MEN5) or sporadic co-occurrences. Distinct clinical disparities exist between the two cohorts. GP-MEN1 patients exhibit an earlier median onset (33-35 years), aggressive and multiglandular disease, and a high probability of developing a third cardinal tumor, leading to a poorer prognosis. Conversely, GN-MEN1 patients present significantly later (46-52 years), rarely develop a third cardinal tumor, and experience a more indolent course with a life expectancy comparable to the general population. In a cohort analysis from National Taiwan University Hospital (NTUH), the paradigm of pitNETs in MEN1 has shifted towards non-functioning microadenomas due to modern screening. GP-MEN1 patients with pitNETs were diagnosed at a younger age, showed higher sellar floor involvement, and had a higher prevalence of adrenal tumors and non-functioning GEP-NENs. In contrast, GN-MEN1 patients were older and more frequently presented with insulinomas. In conclusion, germline mutational status is a critical determinant of MEN1 clinical heterogeneity. Genetic testing is essential not only for confirming diagnoses and facilitating targeted therapies but also for exonerating non-carriers. Although current guidelines recommend uniform surveillance for all MEN1 diagnostic categories, the distinctively indolent phenotype of GN-MEN1 suggests that a modified, de-escalated surveillance approach may be more appropriate and warrants further formal investigation.

Yueh-Ju TsaiTaiwan Moderator

Novel Biomarkers and Treatment Strategies in Thyroid Eye Disease

Chia-Hung LinTaiwan Speaker Novel Biomarkers and Treatment Strategies in Thyroid Eye DiseaseThyroid Eye Disease (TED), also known as Graves' orbitopathy, remains a complex autoimmune condition that significantly impacts patients' vision and quality of life. Traditionally, management has relied mainly on non-specific anti-inflammatory therapies. However, as our understanding of its molecular pathogenesis evolves, there is an increasing clinical demand for more precise diagnostic tools and targeted therapeutic interventions. This presentation provides a comprehensive overview of the current landscape and future directions in the management of TED. We will discuss the emergence of novel serum and molecular biomarkers that offer potential for earlier diagnosis and more accurate prediction of disease progression. These biomarkers may bridge the gap between clinical observation and underlying immunological activity. Furthermore, we will explore the shift in treatment paradigms, moving from conventional systemic corticosteroids toward innovative biological agents. By targeting specific signaling pathways involved in orbital inflammation and remodeling, these new strategies aim to provide more effective and durable clinical outcomes. The integration of novel biomarkers and advanced treatment modalities is reshaping the management of TED. Moving toward a more individualized approach will allow clinicians to optimize therapeutic timing and selection, ultimately improving the long-term prognosis for patients with this challenging condition.
Management of Thyroid Eye Disease: Insights from Clinical Experience and MRI Findings in Japan

Ichiro YamauchiJapan Speaker Management of Thyroid Eye Disease: Insights from Clinical Experience and MRI Findings in JapanIn Japan, disease activity of thyroid eye disease (TED) is commonly assessed using magnetic resonance imaging (MRI) in addition to clinical activity score (CAS). Recently, we proposed an MRI-guided categorization of active moderate-to-severe TED based on our retrospective data. We retrospectively analyzed TED cases treated at our department between 2015 and 2022 with a combination of daily steroid pulse therapy and orbital radiation. Among 44 cases with diplopia, we classified 17 cases as severe (diplopia in the primary position) and 27 as non-severe (diplopia only in non-primary positions). The severe group was older (median 67 years) and had lower TSAb titers (median 324%) compared to the non-severe group (median 56 years, median TSAb 2443%). CAS was similar between the groups. MRI revealed that proptosis was more pronounced in the non-severe group (median 21.4 mm) than in the severe group (median 17.5 mm), whereas the difference in proptosis between eyes was larger in the severe group (median 2.0 mm) than in the non-severe group (median 0.9 mm). High signal intensity of orbital fat on STIR sequence was more frequently observed in the non-severe group (68.2%) than in the severe group (20.0%). These findings suggest that TED patients with severe diplopia are characterized by older age, lower TSAb titers, and greater asymmetry in proptosis. In contrast, CAS and STIR signal intensity of orbital fat were not indicative of severity. In this context, severe diplopia often develops despite low CAS and mild proptosis. We also present our clinical experience with teprotumumab, an anti–IGF-1 receptor antibody. Since its launch in Japan in 2024, we have treated several patients with severe TED, the majority of whom showed remarkable improvement in clinical features. However, adverse effects such as hearing impairment and hyperglycemia were occasionally observed, highlighting the importance of appropriate management. In conclusion, MRI-guided evaluation provides valuable insights for individualized management of TED. Evidence regarding the efficacy of teprotumumab remains limited in the subtype characterized by severe diplopia, which often presents with low CAS and mild proptosis. The MRI-guided approach may help clinicians select optimal therapeutic strategies, including steroid pulse therapy, teprotumumab, and other emerging agents.
Update on Thyroid Eye Disease Management - Asia Pacific Perspectives

Kelvin ChongHong Kong, China Speaker Update on Thyroid Eye Disease Management - Asia Pacific PerspectivesExisting guidelines/recommendations/consensus on the management of thyroid eye disease (TED)/Graves' orbitopathy (GO) pose significant difficulties when applied in the Asia Pacific region. The presenter will share his experiences and challenges in setting up the first thyroid eye clinic in Hong Kong, developing an image-guided medical and surgical decompression, while looking into the future of intelligence-based management of TED/GO.

101