Harn-Shen ChenProf. Taiwan

Harn-Shen ChenProf.
Dr. Harn-Shen Chen is a Professor of Medicine at the National Yang-Ming Chiao-Tung University School of Medicine and an attending physician in the Division of Endocrinology and Metabolism at Taipei Veterans General Hospital, Taiwan. He served as Chief of the Division of Endocrinology and Metabolism at Taipei Veterans General Hospital from 2015 to 2022, during which he led numerous institutional and national initiatives on endocrine and metabolic disorders. Dr. Chen’s clinical practice centers on diabetes mellitus, thyroid diseases, and pituitary disorders, with a strong commitment to integrating clinical excellence, research innovation, and holistic patient care. His research has focused on improving glycemic control, preserving pancreatic beta-cell function in type 2 diabetes, and optimizing the multidisciplinary management of acromegaly. He has also been actively involved in developing national consensus guidelines for acromegaly management in Taiwan, contributing significantly to both patient outcomes and professional education in endocrinology. Internationally, Dr. Chen was a visiting researcher at the University of California, Irvine, where he collaborated on translational studies in diabetes and metabolism. Domestically, he has played key leadership roles in the Endocrine Society of the Republic of China (Taiwan), serving as Secretary General (2013–2016) and currently as Executive Director (since 2022). Through his academic and professional service, Dr. Chen has established himself as one of Taiwan’s leading clinical endocrinologists and educators, dedicated to advancing evidence-based endocrine care and fostering collaboration across Asia in diabetes and pituitary research.

22 MARCH

Time Session
09:10
09:50
Plenary 9
Harn-Shen ChenTaiwan Moderator Acromegaly and Cardiovascular Disease: The Research in Taipei Veterans General HospitalAcromegaly, characterized by chronic excess growth hormone (GH) and elevated insulin-like growth factor-1 (IGF-1), is associated with increased morbidity and premature mortality, particularly from cardiovascular (CV) complications. Research from Taipei Veterans General Hospital (Taipei VGH) over the past decade has systematically examined how biochemical control, metabolic status, and cardiac function influence patient outcomes, forming a comprehensive institutional understanding of acromegaly-related CV risk. Early studies established the prognostic importance of postoperative hormonal normalization following trans-sphenoidal adenomectomy (TSA). Patients achieving stringent biochemical remission demonstrated markedly reduced long-term mortality, whereas persistent GH/IGF-1 elevation remained a strong predictor of premature death. Even partial hormonal improvement provided measurable survival benefit, highlighting the need for aggressive management and close monitoring after surgery. Subsequent work addressed the metabolic impact of medical therapy, particularly long-acting octreotide. While effective in reducing GH/IGF-1 levels, somatostatin analogs impaired insulin secretion and frequently worsened glucose tolerance. These findings underscore the need to balance biochemical control with careful metabolic surveillance, especially in patients with preexisting glucose abnormalities. In 2020, a nationwide epidemiological study expanded the perspective by detailing incidence, comorbidities, re-operation rates, cancer risk, and mortality trends across Taiwan. Despite modern advances, patients with acromegaly continued to exhibit elevated mortality—predominantly from CV and malignant causes—reinforcing the significance of early diagnosis and rigorous long-term management. Complementing epidemiologic insights, a focused clinical study demonstrated that successful surgical remission led to significant improvements in traditional CV risk factors, including reductions in HbA1c, LDL cholesterol, total cholesterol, and blood pressure one year after TSA. These benefits were most pronounced in patients with normalized IGF-1. The most recent study linked degrees of biochemical control to cardiac structure and function. Patients with uncontrolled or partially controlled acromegaly exhibited increased left ventricular mass and impaired diastolic function, indicating early acromegalic cardiomyopathy even when systolic function remained preserved. Collectively, the Taipei VGH research program highlights that full biochemical remission is essential not only for reducing mortality but also for reversing metabolic abnormalities and preventing progressive cardiac dysfunction.
  • Paraneoplastic Autoimmune Hypophysitis: A Novel Form Paraneoplastic Endocrine Syndrome
    Yutaka TakahashiJapan Speaker Paraneoplastic Autoimmune Hypophysitis: A Novel Form Paraneoplastic Endocrine SyndromeThe story begins with a fascinating case we encountered in 2003. It was an outlier of hypopituitarism that presented with acquired deficiencies in GH, PRL, and TSH. We subsequently accumulated similar cases and reported them as a novel disease entity named "anti-PIT-1 hypophysitis." We clarified that this condition represents a paraneoplastic syndrome associated with thymoma or malignancies. The mechanism of onset involves ectopic expression of PIT-1 in the tumor, leading to a breakdown of immune tolerance. As a result, anti-PIT-1 antibodies are produced in the blood, and PIT-1–expressing cells (those producing GH, PRL, and TSH) in the pituitary are damaged by cytotoxic T lymphocytes (CTLs). Recently, we have succeeded in establishing a disease model using co-culture of CTLs and patient-derived iPS cell–generated pituitary cells, demonstrating that CTLs are indeed the causatively involved. Interestingly, we found that a similar mechanism underlies some cases of isolated ACTH deficiency and immune checkpoint inhibitor–related hypophysitis (PD-1/PDL-1-related hypophysitis). Based on this, we proposed a broader new disease concept: “paraneoplastic autoimmune hypophysitis.” Very recently, we discovered a case of “immune checkpoint inhibitor–related anti–PIT-1 hypophysitis,” which clearly supports this concept. To elucidate the pathophysiology of such novel diseases, we emphasize the importance of a cross-disciplinary academic framework—beyond organ-specific medical practice and beyond endocrinology alone—which we refer to as "onco-immuno-endocrinology." In this lecture, I will introduce our research journey and share key insights and lessons for young physician-scientists aiming to reshape the textbooks of the future.Hypophysitis: Difficult CasesHypophysitis is defined as inflammation of the hypothalamo-pituitary region and is classified into primary and secondary forms. Primary hypophysitis refers to autoimmune hypophysitis (lymphocytic hypophysitis) and is essentially a diagnosis by exclusion of other diseases. Secondary hypophysitis can be classified into those associated with local lesions, systemic diseases, or drug-induced causes. Therefore, differential diagnosis from other conditions presenting with similar findings is crucial. Among the secondary forms, immune checkpoint inhibitor–related hypophysitis has emerged. In addition, the newly proposed entity paraneoplastic autoimmune hypophysitis have recently drawn considerable attention. That includes anti-PIT-1 hypophysitis, a component of isolated ACTH deficiency and PD-1/PDL-1-related hypophysitis, in which common mechanism underlies. Ectopic expression of pituitary antigens such as POMC and PIT-1 causes breakdown of immune tolerance and specific cytotoxic T cells injure anterior pituitary cells, results in a specific defect in ACTH or GH, PRL, and TSH, respectively. For systemic diseases, diagnosis proceeds by examining specific disease markers and searching for involvement of other organs. On the other hand, it is often difficult to differentiate lesions confined to the hypothalamo-pituitary region. In atypical cases, pituitary biopsy should be considered. When performing a biopsy, appropriate selection of the biopsy site is essential. If possible, the decision should be made before administering pharmacologic doses of glucocorticoids. In this Meet the Professor session, I would like to provide up-to-date information and foster discussion with audience on key points in the differential diagnosis of hypophysitis, with a focus on immune checkpoint inhibitor–related hypophysitis and paraneoplastic autoimmune hypophysitis, which represent emerging disease concepts.
101
14:00
15:30
[Symposium] Pituitary (3)
Acromegaly
Naoko InoshitaJapan Moderator Consensus in Pituitary Pathology: Impact after New Classification for JapanIn Japan, the brain tumor handling rules are essentially based on the WHO classification. However, the introduction of the term pituitary neuroendocrine tumour (PitNET) has occasionally led to misunderstanding in clinical practice, particularly regarding the implication of malignancy. In this lecture, I will present a consensus-oriented approach in pituitary pathology, focusing on practical strategies developed through multidisciplinary collaboration for the benefit of clinicians and patients. First, I will show how the addition of touch smear cytology to frozen section diagnosis during surgery can improve the accuracy of margin assessment and increase the likelihood of achieving the intended surgical goal, including adequate removal of hormone-producing tumours. Second, I will emphasize that truly malignant PitNETs are extremely rare, and that the term “NET” should not be equated with malignancy. Third, I will discuss the well-known discrepancy between hormone immunohistochemistry and clinical functionality, highlighting the importance of careful pathological interpretation. These perspectives reflect our pathology team’s commitment to accurate communication and clinically relevant pathological diagnosis.
Szu-Tah ChenTaiwan Moderator The Impact of the 2022 WHO PitNET Classification to the Clinical Practitioners. Does Silence Equal Acceptance?The 2022 World Health Organization (WHO) Classification of Endocrine and Neuroendocrine Tumors redefined pituitary adenomas as pituitary neuroendocrine tumors (PitNETs) within the International Classification of Diseases for Oncology, 3rd Edition (ICD-O/3). This change reflects updated insights into tumor biology, recognizing a spectrum of clinical behaviors beyond the traditionally benign designation. A narrative review of the WHO 2022 classification updates was conducted, focusing on their clinical, diagnostic, and epidemiologic implications for practitioners in endocrinology, neurosurgery, and oncology. The reclassification emphasizes the potential for variability in tumor aggressiveness, recurrence, and invasiveness. Clinically, this shift necessitates more careful risk stratification, closer follow-up in selected cases, and a reassessment of treatment algorithms. From a reporting perspective, ICD-O/3 alignment may affect cancer registry data and epidemiologic tracking, altering disease burden estimates. Importantly, the new terminology presents challenges in patient communication, as the label “neuroendocrine tumor” may cause undue anxiety despite the indolent nature of most PitNETs. The WHO 2022 reclassification of pituitary adenomas as PitNETs represents a significant change for clinical practice. While it enhances awareness of potential aggressive behavior, it also requires balanced application in patient care to avoid overtreatment and misperceptions. Practitioners must adapt by refining diagnostic vigilance, tailoring follow-up strategies, and delivering clear patient-centered communication.
  • Acromegaly and Cardiovascular Disease: The Research in Taipei Veterans General Hospital
    Harn-Shen ChenTaiwan Speaker Acromegaly and Cardiovascular Disease: The Research in Taipei Veterans General HospitalAcromegaly, characterized by chronic excess growth hormone (GH) and elevated insulin-like growth factor-1 (IGF-1), is associated with increased morbidity and premature mortality, particularly from cardiovascular (CV) complications. Research from Taipei Veterans General Hospital (Taipei VGH) over the past decade has systematically examined how biochemical control, metabolic status, and cardiac function influence patient outcomes, forming a comprehensive institutional understanding of acromegaly-related CV risk. Early studies established the prognostic importance of postoperative hormonal normalization following trans-sphenoidal adenomectomy (TSA). Patients achieving stringent biochemical remission demonstrated markedly reduced long-term mortality, whereas persistent GH/IGF-1 elevation remained a strong predictor of premature death. Even partial hormonal improvement provided measurable survival benefit, highlighting the need for aggressive management and close monitoring after surgery. Subsequent work addressed the metabolic impact of medical therapy, particularly long-acting octreotide. While effective in reducing GH/IGF-1 levels, somatostatin analogs impaired insulin secretion and frequently worsened glucose tolerance. These findings underscore the need to balance biochemical control with careful metabolic surveillance, especially in patients with preexisting glucose abnormalities. In 2020, a nationwide epidemiological study expanded the perspective by detailing incidence, comorbidities, re-operation rates, cancer risk, and mortality trends across Taiwan. Despite modern advances, patients with acromegaly continued to exhibit elevated mortality—predominantly from CV and malignant causes—reinforcing the significance of early diagnosis and rigorous long-term management. Complementing epidemiologic insights, a focused clinical study demonstrated that successful surgical remission led to significant improvements in traditional CV risk factors, including reductions in HbA1c, LDL cholesterol, total cholesterol, and blood pressure one year after TSA. These benefits were most pronounced in patients with normalized IGF-1. The most recent study linked degrees of biochemical control to cardiac structure and function. Patients with uncontrolled or partially controlled acromegaly exhibited increased left ventricular mass and impaired diastolic function, indicating early acromegalic cardiomyopathy even when systolic function remained preserved. Collectively, the Taipei VGH research program highlights that full biochemical remission is essential not only for reducing mortality but also for reversing metabolic abnormalities and preventing progressive cardiac dysfunction.
  • Medication Management for Acromegaly
    Cheol Ryong KuSouth Korea Speaker Medication Management for AcromegalyPharmacological management of acromegaly plays a central role in patients with persistent disease following surgery; however, treatment strategies vary substantially across countries due to differences in healthcare systems and reimbursement policies. Understanding real-world approaches within specific national frameworks provides valuable insight into optimizing long-term disease control. This lecture aims to present the Korean reimbursement-based treatment algorithm for acromegaly and share institutional clinical outcomes using contemporary medical therapies, including pasireotide, pegvisomant, and lanreotide autogel with extended dosing interval (EDI) strategies. In addition, emerging therapeutic candidates under development at our institution will be briefly introduced.
  • Acromegaly: GH Response Pattern to Oral Glucose Load and Personalized Medicine
    Michio OtsukiJapan Speaker Acromegaly: GH Response Pattern to Oral Glucose Load and Personalized MedicineAcromegaly is characterized by elevated levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1), with resultant signs and symptoms of hypersomatotropism. To examine autonomous secretion of GH, an oral glucose tolerance test (OGTT) is used. In most healthy individuals, GH levels decrease to a nadir below 0.4 mg/L after OGTT. In contrast, patients with acromegaly fail to suppress serum GH levels after OGTT. Interestingly, a paradoxical GH response to oral glucose (OG) load is found in one third of acromegalic patients. The mechanism of this paradoxical response in acromegaly is mediated by glucose-dependent insulinotropic polypeptide, which is released after OG administration We found that the paradoxical GH response to OG load reflected the clinical characteristics. The patients the paradoxical GH response to OG load (OG responders) had substantially greater IGF-1 SD scores than nonresponders. Regarding glucose metabolism, 120-minute plasma glucose and immunoreactive insulin after OG administration and hemoglobin A1c were significantly greater in OG responders than in nonresponders. GH levels during octreotide or bromocriptine testing were decreased more significantly in OG responders than in nonresponder. The proportion of pituitary tumors with hypointensity on T2-weighted MRI was significantly greater in OG responders than in nonresponders. OGTT is essential to evaluate autonomous secretion of GH. The paradoxical GH response to OG load is the useful for evaluation of the clinical characteristics of acromegaly and leads to the personalized medicine of acromegaly.
201DE