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Hiroshi Arima 3 Articles
Diabetes, Obesity and Metabolism
Human Leukocyte Antigens and Biomarkers in Type 1 Diabetes Mellitus Induced by Immune-Checkpoint Inhibitors
Hidefumi Inaba, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Takakazu Sugita, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, Takaaki Matsuoka
Endocrinol Metab. 2022;37(1):84-95.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2021.1282
  • 6,330 View
  • 191 Download
  • 23 Web of Science
  • 23 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear.
Methods
In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021.
Results
Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset.
Conclusion
Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

Citations

Citations to this article as recorded by  
  • Immune checkpoint inhibitor‐related type 1 diabetes incidence, risk, and survival association
    Fumika Kamitani, Yuichi Nishioka, Miyuki Koizumi, Hiroki Nakajima, Yukako Kurematsu, Sadanori Okada, Shinichiro Kubo, Tomoya Myojin, Tatsuya Noda, Tomoaki Imamura, Yutaka Takahashi
    Journal of Diabetes Investigation.2025; 16(2): 334.     CrossRef
  • Immune checkpoint inhibitor-related diabetes mellitus associated with high signal intensity in diffusion-weighted magnetic resonance imaging of the pancreas at an early clinical stage
    Masaki Suzuki, Yushi Hirota, Shin Urai, Masaaki Yamamoto, Keitaro Sofue, Wataru Ogawa
    Hormones.2025;[Epub]     CrossRef
  • Durvalumab-induced Type 1 Diabetes in a Patient With Pre-existing GADA-positive Diabetes and Preserved Insulin Secretion
    Nobuhiro Nakatake, Megumi Matsuda, Hiroki Kontani
    JCEM Case Reports.2025;[Epub]     CrossRef
  • Machine-Learning Parsimonious Prediction Model for Diagnostic Screening of Severe Hematological Adverse Events in Cancer Patients Treated with PD-1/PD-L1 Inhibitors: Retrospective Observational Study by Using the Common Data Model
    Seok Jun Park, Seungwon Yang, Suhyun Lee, Sung Hwan Joo, Taemin Park, Dong Hyun Kim, Hyeonji Kim, Soyun Park, Jung-Tae Kim, Won Gun Kwack, Sung Wook Kang, Yun-Kyoung Song, Jae Myung Cha, Sang Youl Rhee, Eun Kyoung Chung
    Diagnostics.2025; 15(2): 226.     CrossRef
  • Type 1 diabetes mellitus affected by potential toxicity from long-term use of nivolumab
    Yuma Motomura, Shin Urai, Yushi Hirota, Naoki Takegawa, Hironori Bando, Masaaki Yamamoto, Hidenori Fukuoka, Masahiro Tsuda, Wataru Ogawa
    Diabetology International.2024; 15(1): 130.     CrossRef
  • Review – The impact of pharmacogenetics on the outcome of immune checkpoint inhibitors
    Karlijn de Joode, Niels Heersche, Edwin A. Basak, Sander Bins, Astrid A.M. van der Veldt, Ron H.N. van Schaik, Ron H.J. Mathijssen
    Cancer Treatment Reviews.2024; 122: 102662.     CrossRef
  • Case report: Strong GAD antibody positivity and type 1 diabetes-HLA-susceptible haplotype-DRB1*04:05-DQB1*04:01 in a Japanese patient with immune checkpoint inhibitor-induced type 1 diabetes
    Shunya Yabuki, Hiroyuki Hirai, Chihiro Moriya, Yoshiro Kusano, Takeo Hasegawa
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Reaching the Diagnosis of Checkpoint Inhibitor-Induced Diabetes Mellitus in Different Clinical Scenarios: A Real-World Application of Updated Diagnostic Criteria
    Anna Angelousi, Dimitrios C. Ziogas, Vasiliki Siampanopoulou, Chrysoula Mytareli, Amalia Anastasopoulou, George Lyrarakis, Helen Gogas
    Diseases.2024; 12(2): 40.     CrossRef
  • Non-Invasive Predictive Biomarkers for Immune-Related Adverse Events Due to Immune Checkpoint Inhibitors
    Ben Ponvilawan, Abdul Wali Khan, Janakiraman Subramanian, Dhruv Bansal
    Cancers.2024; 16(6): 1225.     CrossRef
  • A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab
    Kota Nishihama, Yuko Okano, Chisa Inoue, Kanako Maki, Kazuhito Eguchi, Soichiro Tanaka, Atsuro Takeshita, Mei Uemura, Taro Yasuma, Toshinari Suzuki, Esteban C. Gabazza, Yutaka Yano
    Diabetology International.2024; 15(3): 583.     CrossRef
  • HLA investigation in ICI-induced T1D and isolated ACTH deficiency including meta-analysis
    Mayo Ono, Mototsugu Nagao, Haruki Takeuchi, Etsuya Fukunaga, Tomoko Nagamine, Kyoko Inagaki, Izumi Fukuda, Masato Iwabu
    European Journal of Endocrinology.2024; 191(1): 9.     CrossRef
  • Pathophysiology, diagnosis, and management of immune checkpoint inhibitor-induced diabetes mellitus
    Eleni-Rafaela Kani, Eleftheria Karaviti, Dimitra Karaviti, Eleni Gerontiti, Ioanna A. Paschou, Katerina Saltiki, Katerina Stefanaki, Theodora Psaltopoulou, Stavroula A. Paschou
    Endocrine.2024; 87(3): 875.     CrossRef
  • A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome
    John Marsiglio, Jordan P. McPherson, Magdalena Kovacsovics-Bankowski, Joanne Jeter, Christos Vaklavas, Umang Swami, Douglas Grossmann, Alyssa Erickson-Wayman, Heloisa P. Soares, Katie Kerrigan, Berit Gibson, Jennifer Anne Doherty, John Hyngstrom, Sheetal
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Predictive Biomarkers for Immune-Related Endocrinopathies following Immune Checkpoint Inhibitors Treatment
    Almog Shalit, Panagiotis Sarantis, Evangelos Koustas, Eleni-Myrto Trifylli, Dimitris Matthaios, Michalis V. Karamouzis
    Cancers.2023; 15(2): 375.     CrossRef
  • Predictive Biomarkers for Checkpoint Inhibitor Immune-Related Adverse Events
    Iñigo Les, Mireia Martínez, Inés Pérez-Francisco, María Cabero, Lucía Teijeira, Virginia Arrazubi, Nuria Torrego, Ana Campillo-Calatayud, Iñaki Elejalde, Grazyna Kochan, David Escors
    Cancers.2023; 15(5): 1629.     CrossRef
  • Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors
    Hidefumi Inaba, Shuhei Morita, Daisuke Kosugi, Yuki Asai, Yosuke Kaido, Saya Ito, Tomonao Hirobata, Gen Inoue, Yuki Yamamoto, Masatoshi Jinnin, Hiroaki Kimura, Masao Ota, Yuko Okudaira, Hiroyasu Nakatani, Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima, T
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Clinical characteristics and human leukocyte antigens in patients with immune checkpoint inhibitor-induced type 1 diabetes and pituitary dysfunction: a single center prospective study
    Natsuko Hara, Hirotsugu Suwanai, Fumiyoshi Yakou, Keitaro Ishii, Hajime Iwasaki, Hironori Abe, Jumpei Shikuma, Hiroyuki Sakai, Takashi Miwa, Ryo Suzuki
    Endocrine.2023; 81(3): 477.     CrossRef
  • Autoimmunity in immune checkpoint inhibitor‐induced immune‐related adverse events: A focus on autoimmune skin toxicity and pneumonitis
    Fiamma Berner, Lukas Flatz
    Immunological Reviews.2023; 318(1): 37.     CrossRef
  • Prediction-based prompt levothyroxine replacement to prevent a hypothyroid state after immune-related adverse events involving the thyroid gland
    Ichiro Yamauchi, Takuro Hakata, Taku Sugawa, Daisuke Kosugi, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Norio Harada, Nobuya Inagaki
    Endocrine Journal.2023; 70(10): 987.     CrossRef
  • Key Determinants of Immune-Mediated Adverse Reactions to Oncology Drugs
    Yihan Zhou, Shan Ding
    Cancers.2023; 15(23): 5622.     CrossRef
  • Risk factors and predictors of immune-related adverse events: implications for patients with non-small cell lung cancer
    Majd Issa, Joy Tang, Yizhen Guo, Chris Coss, Thomas A. Mace, Jason Bischof, Mitch Phelps, Carolyn J Presley, Dwight H Owen
    Expert Review of Anticancer Therapy.2022; 22(8): 861.     CrossRef
  • Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors
    Adithya Chennamadhavuni, Laith Abushahin, Ning Jin, Carolyn J. Presley, Ashish Manne
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Flash Glucose Monitoring and Diabetes Mellitus Induced by Immune Checkpoint Inhibitors: An Approach to Clinical Practice
    Pablo Rodríguez de Vera-Gómez, Ana Piñar-Gutiérrez, Raquel Guerrero-Vázquez, Virginia Bellido, Cristóbal Morales-Portillo, María Pilar Sancho-Márquez, Pablo Espejo-García, Noelia Gros-Herguido, Gema López-Gallardo, María Asunción Martínez-Brocca, Alfonso
    Journal of Diabetes Research.2022; 2022: 1.     CrossRef
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Miscellaneous
Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors
Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
Endocrinol Metab. 2021;36(2):312-321.   Published online April 27, 2021
DOI: https://doi.org/10.3803/EnM.2021.1007
  • 7,871 View
  • 298 Download
  • 24 Web of Science
  • 22 Crossref
AbstractAbstract PDFPubReader   ePub   
Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Citations

Citations to this article as recorded by  
  • Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors
    Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
    Nature Reviews Endocrinology.2025;[Epub]     CrossRef
  • Thyroid Dysfunction After Intensity-Modulated Radiotherapy and PD⁃1 Inhibitor Treatment for Locally Advanced Nasopharyngeal Carcinoma
    Kai Shang, Qianyong He, Xinyu Xu, Xunyan Luo, Chaofen Zhao, Lina Liu, Zhuoling Li, Yuanyuan Li, Feng Jin
    Therapeutics and Clinical Risk Management.2025; Volume 21: 15.     CrossRef
  • Subacute thyroiditis during anti-programmed cell death protein 1 antibody therapy: A case report
    Makiko Ikemoto, Yasufumi Seki, Daisuke Watanabe, Toshio Takagi, Atsuhiro Ichihara
    Thyroid Science.2025; 2(2): 100024.     CrossRef
  • Clinical characteristics and potential biomarkers of thyroid and pituitary immune-related adverse events
    Tomoko Kobayashi, Shintaro Iwama, Hiroshi Arima
    Endocrine Journal.2024; 71(1): 23.     CrossRef
  • A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab
    Kota Nishihama, Yuko Okano, Chisa Inoue, Kanako Maki, Kazuhito Eguchi, Soichiro Tanaka, Atsuro Takeshita, Mei Uemura, Taro Yasuma, Toshinari Suzuki, Esteban C. Gabazza, Yutaka Yano
    Diabetology International.2024; 15(3): 583.     CrossRef
  • Endocrinopathies Associated With Immune Checkpoint Inhibitor Use
    Anupam Kotwal, Randol Kennedy, Nupur Kikani, Sonali Thosani, Whitney Goldner, Afreen Shariff
    Endocrine Practice.2024; 30(6): 584.     CrossRef
  • Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study
    Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Tetsushi Izuchi, Koji Suzuki, Koki Otake, Yoshinori Yasuda, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Naoki Nishio, Shoi
    Cancer Immunology, Immunotherapy.2024;[Epub]     CrossRef
  • Adrenal Insufficiency and Thyrotoxicosis Following Combined Immune Checkpoint Inhibitor Use: A Case Report and Literature Review
    Kaoruko Fukushima, Saori Kitayama, Manami Sazuka, Remi Kodera, Kazuhito Oba, Kenji Toyoshima, Yuko Chiba, Hiroshi Yamamoto, Atsushi Araki, Yoshiaki Tamura
    Cureus.2024;[Epub]     CrossRef
  • Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade
    Ayana Yamagami, Shintaro Iwama, Tomoko Kobayashi, Xin Zhou, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Tetsushi Izuchi, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima
    Endocrine Journal.2024; 71(5): 515.     CrossRef
  • Single-cell RNA sequencing analysis of peripheral blood mononuclear cells in PD-1-induced renal toxicity in patients with lung cancer
    Shusu Liu, Peiyu Lu, Bixia Yang, Yan Yang, Hua Zhou, Min Yang
    BMC Nephrology.2024;[Epub]     CrossRef
  • Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
    Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Koki Otake, Masahiko Ando, Tomoko Handa, Takashi Miyata, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Megumi Inoue, Makoto Ishii, Hiroshi Arima, Shintaro Iw
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report
    Marie Okubo, Yuji Hataya, Kanta Fujimoto, Toshio Iwakura, Naoki Matsuoka
    Journal of Diabetes Investigation.2023; 14(1): 147.     CrossRef
  • Case Report: A Rising Cause of New-Onset Endocrinopathies After Immunotherapy
    Charity Tan, Sarah Hendricks, Kristina Hernandez, Martha Benavides, Rupinderjit Samra
    The Journal for Nurse Practitioners.2023; 19(5): 104582.     CrossRef
  • Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline
    Xin Zhou, Shintaro Iwama, Tomoko Kobayashi, Masahiko Ando, Hiroshi Arima
    The Journal of Clinical Endocrinology & Metabolism.2023; 108(10): e1056.     CrossRef
  • Severe thyrotoxicosis induced by tislelizumab: a case report and literature review
    Liman Huo, Chao Wang, Haixia Ding, Xuelian Shi, Bin Shan, Ruoying Zhou, Ping Liang, Juan Hou
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Life-Threatening Endocrinological Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy
    Aleksandra Basek, Grzegorz K. Jakubiak, Grzegorz Cieślar, Agata Stanek
    Cancers.2023; 15(24): 5786.     CrossRef
  • Increased Risk of Thyroid Dysfunction by PD-1 and CTLA-4 Blockade in Patients Without Thyroid Autoantibodies at Baseline
    Shintaro Iwama, Tomoko Kobayashi, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Masahiko Ando, Xin Zhou, Ayana Yamagami, Takeshi Onoue, Yohei Kawaguchi, Takashi Miyata, Mariko Sugiyama, Hiroshi Takagi, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tets
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(4): e1620.     CrossRef
  • Biomarkers and risk factors for the early prediction of immune-related adverse events: a review
    Ying Zhang, Xiaoling Zhang, Weiling Li, Yunyi Du, Wenqing Hu, Jun Zhao
    Human Vaccines & Immunotherapeutics.2022;[Epub]     CrossRef
  • Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle
    Agnese Barnabei, Andrea Corsello, Rosa Maria Paragliola, Giovanni Maria Iannantuono, Luca Falzone, Salvatore Maria Corsello, Francesco Torino
    Cancers.2022; 14(4): 1057.     CrossRef
  • Elevated TSH Level, TgAb, and Prior Use of Ramucirumab or TKIs as Risk Factors for Thyroid Dysfunction in PD-L1 Blockade
    Tomoko Kobayashi, Shintaro Iwama, Ayana Yamagami, Yoshinori Yasuda, Takayuki Okuji, Masaaki Ito, Xin Zhou, Masahiko Ando, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Masahiro Morise, Taka
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(10): e4115.     CrossRef
  • Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors
    Fabiana Pani, Yoshinori Yasuda, Sylvie T Rousseau, Kevin C Bermea, Solmaz Roshanmehr, Rulin Wang, Srinivasan Yegnasubramanian, Patrizio Caturegli, Luigi Adamo
    Journal for ImmunoTherapy of Cancer.2022; 10(12): e005538.     CrossRef
  • Survival benefit of endocrine dysfunction following immune checkpoint inhibitors for nonthyroidal cancers
    Anupam Kotwal, Mabel Ryder
    Current Opinion in Endocrinology, Diabetes & Obesity.2021; 28(5): 517.     CrossRef
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Combined PD-1 and CTLA-4 Blockade Increases the Risks of Multiple Pituitary Hormone Deficiency and Isolated Adrenocorticotropic Deficiency: A Prospective Study
Shintaro Iwama, Tomoko Kobayashi, Tetsushi Izuchi, Koji Suzuki, Takanori Murase, Masahiko Ando, Tomoko Handa, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Shoichiro Mori, Tomoyasu Sano, Shusuke Akamatsu, Masashi Akiyama, Makoto Ishii, Hiroshi Arima
Received September 24, 2024  Accepted November 18, 2024  Published online February 11, 2025  
DOI: https://doi.org/10.3803/EnM.2024.2180    [Epub ahead of print]
  • 628 View
  • 31 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) monotherapy induces two types of pituitary immunerelated adverse events (irAEs): multiple pituitary hormone deficiency (Multi-D; impairment of ≥2 anterior pituitary hormones) and isolated adrenocorticotropic hormone (ACTH) deficiency (IAD). Combination therapy with CTLA-4-Ab and anti-programmed cell death-1 antibody (PD-1/CTLA-4-Abs), which is increasingly replacing CTLA-4-Ab monotherapy, frequently causes pituitary irAEs; however, whether it increases Multi-D/IAD incidence is unknown.
Methods
In total, 74 and 748 patients with malignancies treated with PD-1/CTLA-4-Abs and PD-1-Ab, respectively, were prospectively evaluated for ACTH and cortisol levels at baseline and every 6 weeks after treatment initiation, and then observed until the last clinical visit. The characteristics of pituitary irAEs were evaluated by pituitary stimulation tests and compared with those induced by PD-1-Ab monotherapy.
Results
PD-1/CTLA-4-Abs therapy showed higher incidence rates of pituitary irAEs (16/74 [21.6%] vs. 25/748 [3.3%], P<0.001), Multi-D (9/74 [12.2%] vs. 2/748 [0.3%], P<0.001), and IAD (7/74 [9.5%] vs. 23/748 [3.1%], P=0.014) than PD-1-Ab monotherapy. ACTH deficiency was observed in all cases, whereas the prevalence rates of luteinizing hormone deficiency (8/16 [50.0%] vs. 1/25 [4.0%]), follicle-stimulating hormone deficiency (6/16 [37.5%] vs. 1/25 [4.0%]), and thyrotropin deficiency (4/16 [25.0%] vs. 0/25 [0%]) were significantly higher after PD-1/CTLA-4-Abs than after PD-1-Ab treatment. Pituitary enlargement, which was observed only in the Multi-D cases, was significantly more frequent after PD-1/CTLA-4-Abs than after PD-1-Ab treatment (6/16 [37.5%] vs. 0/25 [0%], P=0.002).
Conclusion
This prospective study revealed high risks of both Multi-D and IAD under PD-1/CTLA-4-Abs treatment, emphasizing the need for careful evaluation of pituitary function.
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