Shyang-Rong Shih Taiwan

• 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.

• PitNET in Multiple Endocrine Neoplasm
  Sang Ouk ChinCanada Speaker PitNET in Multiple Endocrine NeoplasmMultiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal-dominant syndrome involving neoplasms of the parathyroid glands, pituitary gland, and endocrine components of the gastrointestinal system. Pituitary neuroendocrine tumors (PitNETs) develop in roughly 40% of individuals with MEN1 and constitute the initial clinical presentation in approximately 10% of cases. Recent epidemiological data indicate a modest female predominance, with tumors smaller than 1 cm occurring more frequently than larger lesions. Hormone-secreting PitNETs are observed more often than non-functioning tumors, representing nearly 36–48% of cases, and prolactin-secreting adenomas remain the most prevalent subtype. In comparison with sporadic PitNETs, those associated with MEN1 are more likely to exhibit plurihormonal secretion, greater tumor size, and locally aggressive behavior, while age at diagnosis and the relative frequency of functional tumors appear comparable. Patients lacking detectable MEN1 gene mutations often present with larger and more clinically apparent PitNETs at diagnosis. Although rare, pituitary carcinoma has been documented in six patients with MEN1, including one individual without an identifiable MEN1 mutation. Current evidence suggests that management strategies for MEN1-related PitNETs largely parallel those used for sporadic tumors. PitNETs have also been described in multiple endocrine neoplasia type 4 (MEN4), though comprehensive epidemiologic characterization remains limited, and MEN4 should be considered in patients with MEN1-like clinical features and negative MEN1 genetic testing.
• Oncologist Perspective of NET Management
  Stephen ChanHong Kong, China Speaker Oncologist Perspective of NET Management
• The impact of mutational status on the heterogeneity of MEN1
  Shyang-Rong ShihTaiwan Speaker 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.