Yutaka TakahashiProf. Japan

Yutaka TakahashiProf.
He is a professor at the Division of Diabetes and Endocrinology, Nara Medical University since 2020. He received PhD in 1996 at Kobe University. His research interests include case-oriented or disease-oriented research, especially in the field of pituitary and adrenal diseases. Within his work, his group has established the novel clinical entity, “paraneoplastic autoimmune hypophysitis”, which includes anti-PIT-1 hypophysitis, a component of isolated adrenocorticotropic hormone (ACTH) deficiency and immune checkpoint inhibitor-related hypophysitis. Also, his group reported the association of adult growth hormone deficiency and MASLD/MASH and the first application of iPS cells for pituitary disease modeling. He has contributed for international guidelines of the pituitary and adrenal diseases (Cushing disease; Lancet Diabetes and Endocrinol 2021, Cushing syndrome; Nature Disease Primers 2025, and Pituitary incidentaloma; Nature Rev Endocirinol 2025) as well as Japanese Clinical Practice Guideline for Hypothalamic-Pituitary Dysfunction and Congenital Nephrogenic Diabetes Insipidus and Related Disorders, 2023. He serves the President of the Pituitary Society (2025-2026), the managing director of the Japan Endocrine Society, and the Japan Neuroendocrine Society, and is also board member of the Japanese Society for Hypothalamic and Pituitary Disease.

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
13:30
14:00
Meet the Professor 8
Pituitary
Ming-Nan ChienTaiwan Moderator
  • Hypophysitis: Difficult Cases
    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.
201DE