研究者詳細 - 岩間　信太郎

論文 - 岩間　信太郎

分割表示 103 件中 1 - 20 件目／全件表示 >>

Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors 査読有り国際誌

Iwama, S; Kobayashi, T; Arima, H

NATURE REVIEWS ENDOCRINOLOGY 2025年1月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Reviews Endocrinology

Immune-related adverse events (irAEs), including endocrine irAEs, can occur in response to cancer immunotherapy using immune checkpoint inhibitors (ICIs). Of the endocrine irAEs, pituitary and thyroid irAEs are most frequently observed, followed by primary adrenal insufficiency, type 1 diabetes mellitus and hypoparathyroidism. Notably, pituitary irAEs and type 1 diabetes mellitus can be lethal if overlooked, potentially leading to adrenal crisis and diabetic ketoacidosis, respectively. On the other hand, pituitary and thyroid irAEs are reported to be associated with more favourable prognoses in some cancers if treated appropriately with hormone-replacement therapies. It would be useful to identify those people who are likely to develop endocrine irAEs before initiating therapy with ICIs. Anti-pituitary antibodies and thyroid autoantibodies have been identified as potential biomarkers for the development of pituitary and thyroid irAEs, respectively. This Review elaborates on the clinical characteristics and management strategies of several endocrine irAEs, using the latest research findings and guidelines published by several academic societies.

DOI： 10.1038/s41574-024-01077-6

Continuous glucose monitoring with low-glucose alerts in insulin-treated drivers with diabetes: A randomized crossover study. 査読有り国際誌

Maeda R, Onoue T, Mizutani K, Suzuki K, Handa T, Kobayashi T, Iwama S, Miyata T, Sugiyama M, Hagiwara D, Suga H, Kinoshita F, Arima H

Diabetes research and clinical practice 頁： 112074 2025年2月

Dapagliflozin increased pancreatic beta cell proliferation and insulinogenic index in mice fed a high-fat and high-sodium chloride diet 査読有り国際誌

Hirose, T; Takagi, H; Kuno, M; Sasaki, T; Taki, K; Ito, Y; Miyata, T; Kobayashi, T; Sugiyama, M; Onoue, T; Hagiwara, D; Iwama, S; Suga, H; Banno, R; Arima, H

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 749 巻頁： 151364 - 151364 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biochemical and Biophysical Research Communications

People in Eastern Asia, including Japan, traditionally consume higher amounts of sodium chloride than in the United States and Western Europe, and it is common knowledge that impaired insulin secretion—rather than insulin resistance—is highly prevalent in Asian people who have diabetes mellitus. We previously reported that mice fed a high-fat and high-sodium chloride (HFHS) diet had a relatively lower degree of obesity than mice fed a high-fat diet, but had a comparatively impaired insulin secretion. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to dampen down the sympathetic nervous system, which reportedly is activated by a high-sodium chloride diet. In this study, we examined the effects of dapagliflozin, a SGLT2 inhibitor, on glucose metabolism and insulin secretion in mice fed a HFHS diet. C57BL6/J mice were fed a HFHS diet for 6 weeks and subsequently divided into two treatment groups fed: (1) a HFHS diet mixed with dapagliflozin for up to 3 weeks (HFHS + Da) and (2) a HFHS diet without dapagliflozin (HFHS). Dapagliflozin improved glucose tolerance and the insulinogenic index accompanied by increased pancreatic beta cell proliferation. Furthermore, dapagliflozin decreased both the tyrosine hydroxylase-positive area in pancreatic islets and catecholamine excretion in urine. Our results suggest that dapagliflozin improved insulin secretion by suppressing sympathetic nerve activation in mice fed a HFHS diet.

DOI： 10.1016/j.bbrc.2025.151364

Combined PD-1 and CTLA-4 Blockade Increases the Risks of Multiple Pituitary Hormone Deficiency and Isolated Adrenocorticotropic Deficiency: A Prospective Study. 査読有り国際誌

Iwama S, Kobayashi T, Izuchi T, Suzuki K, Murase T, Ando M, Handa T, Onoue T, Miyata T, Sugiyama M, Hagiwara D, Suga H, Banno R, Hase T, Mori S, Sano T, Akamatsu S, Akiyama M, Ishii M, Arima H

Endocrinology and metabolism (Seoul, Korea) 2025年2月

Compensatory mechanisms underlying arginine vasopressin regulation in transient polyuria during pregnancy 査読有り国際誌

Tsumura, T; Hagiwara, D; Naito, S; Kondo, Y; Kawaguchi, Y; Miyata, T; Kobayashi, T; Sugiyama, M; Onoue, T; Iwama, S; Suga, H; Banno, R; Arima, H

PEPTIDES 184 巻頁： 171352 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Peptides

Transient polyuria during pregnancy is reportedly caused by increased arginine vasopressin (AVP) degradation due to vasopressinase produced by the placenta. The mechanism underlying transient polyuria during pregnancy has not been established. In this study we measured urine volume, urine osmolality, and AVP transcriptional activity during pregnancy in wild-type and familial neurohypophysial diabetes insipidus (FNDI) mice. The FNDI mice were used as a partial AVP deficiency model. Vasopressinase was shown to be present in the placentas of pregnant mice. The Avp hnRNA level in the supraoptic nucleus, which is indicative of AVP transcriptional activity, was upregulated in wild-type and FNDI mice during late pregnancy. FNDI mice, but not wild-type mice, had a significant increase in urine volume and a decrease in urine osmolality during pregnancy. These data suggest that an increase in urine volume during pregnancy only occurs when the compensatory increase in AVP release is insufficient to counteract degradation by vasopressinase.

DOI： 10.1016/j.peptides.2025.171352

Guidance on Energy Intake Based on Resting Energy Expenditure and Physical Activity: Effective for Reducing Body Weight in Patients with Obesity 査読有り国際誌

Handa, T; Onoue, T; Maeda, R; Mizutani, K; Suzuki, K; Kobayashi, T; Miyata, T; Sugiyama, M; Hagiwara, D; Iwama, S; Suga, H; Banno, R; Arima, H

NUTRIENTS 17 巻 ( 2 ) 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nutrients

Objective: In treating obesity, energy intake control is essential to avoid exceeding energy expenditure. However, excessive restriction of energy intake often leads to resting energy expenditure (REE) reduction, increasing hunger and making weight loss difficult. This study aimed to investigate whether providing nutritional guidance that considers energy expenditure based on the regular evaluation of REE and physical activity could effectively reduce body weight (BW) in patients with obesity. Methods: A single-arm, prospective interventional study was conducted on 20 patients with obesity (body mass index ≥ 25 kg/m2) at the Nagoya University Hospital for 24 weeks. REE and physical activity were regularly assessed, and the recommended energy intake was adjusted based on the values. The primary outcome was the change in BW, and the secondary outcomes included changes in REE and hunger ratings, which were assessed using a visual analog scale. Results: Eighteen participants completed the study, demonstrating a significant reduction in BW after 24 weeks (−5.34 ± 6.76%, p < 0.0001). No significant changes were observed in REE or hunger ratings. No adverse events were reported throughout the study period. Conclusions: Guidance on energy intake based on REE and physical activity was effective for reducing BW in patients with obesity without decreasing REE or increasing hunger. This approach may reduce the burden on patients with obesity while losing BW.

DOI： 10.3390/nu17020202

A deep learning approach to predict differentiation outcomes in hypothalamic-pituitary organoids 査読有り国際誌

Asano, T; Suga, H; Niioka, H; Yukawa, H; Sakakibara, M; Taga, S; Soen, M; Miwata, T; Sasaki, H; Seki, T; Hasegawa, S; Murakami, S; Abe, M; Yasuda, Y; Miyata, T; Kobayashi, T; Sugiyama, M; Onoue, T; Hagiwara, D; Iwama, S; Baba, Y; Arima, H

COMMUNICATIONS BIOLOGY 7 巻 ( 1 ) 頁： 1468 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Communications Biology

We use three-dimensional culture systems of human pluripotent stem cells for differentiation into pituitary organoids. Three-dimensional culture is inherently characterized by its ability to induce heterogeneous cell populations, making it difficult to maintain constant differentiation efficiency. That is why the culture process involves empirical aspects. In this study, we use deep-learning technology to create a model that can predict from images of organoids whether differentiation is progressing appropriately. Our models using EfficientNetV2-S or Vision Transformer, employing VENUS-coupled RAX expression, predictively class bright-field images of organoids into three categories with 70% accuracy, superior to expert-observer predictions. Furthermore, the model obtained by ensemble learning with the two algorithms can predict RAX expression in cells without RAX::VENUS, suggesting that our model can be deployed in clinical applications such as transplantation.

DOI： 10.1038/s42003-024-07109-1

その他リンク： https://www.nature.com/articles/s42003-024-07109-1

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 査読有り国際誌

Suzuki, K; Kobayashi, T; Izuchi, T; Otake, K; Ando, M; Handa, T; Miyata, T; Sugiyama, M; Onoue, T; Hagiwara, D; Suga, H; Banno, R; Hase, T; Inoue, M; Ishii, M; Arima, H; Iwama, S

FRONTIERS IN ENDOCRINOLOGY 15 巻頁： 1490042 - 1490042 2024年11月

担当区分：最終著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Frontiers in Endocrinology

Background: Immune-related adverse events (irAEs) are reported to be associated with better overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors. However, there may be a bias in that patients who develop irAEs must survive long enough to experience the irAEs, and no prospective studies adjusting for immortal time bias (ITB) have examined the relationship between OS and pituitary dysfunction or the two different types of thyroid dysfunction: destructive thyroiditis and hypothyroidism without prior thyrotoxicosis (isolated hypothyroidism). Methods: Patients with NSCLC who received nivolumab or pembrolizumab at Nagoya University Hospital between November 2, 2015 and February 1, 2023 were enrolled. Endocrine irAEs were prospectively assessed during scheduled evaluations of hormone levels. The association between irAE development and survival when considering ITB was examined by time-dependent Cox regression analysis. Results: Of the 194 patients included, 11 (5.7%), 10 (5.2%), and 5 (2.6%) developed pituitary dysfunction, destructive thyroiditis, and isolated hypothyroidism, respectively. The development of pituitary dysfunction (HR 0.36, 95% CI 0.13–0.98, p = 0.045) and destructive thyroiditis (HR 0.31, 95% CI 0.10–0.97, p = 0.044), but not isolated hypothyroidism (HR 1.15, 95% CI 0.42–3.20, p = 0.786), was significantly associated with longer OS. Conclusion: NSCLC patients developing pituitary dysfunction and destructive thyroiditis showed better OS even after adjusting for ITB, suggesting that these irAEs indicate a better prognosis.

DOI： 10.3389/fendo.2024.1490042

Voluntary exercise suppresses inflammation and improves insulin resistance in the arcuate nucleus and ventral tegmental area in mice on a high-fat diet 査読有り国際誌

Sasaki T., Sugiyama M., Kuno M., Miyata T., Kobayashi T., Yasuda Y., Onoue T., Takagi H., Hagiwara D., Iwama S., Suga H., Banno R., Arima H.

Physiology and Behavior 287 巻頁： 114703 - 114703 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Physiology and Behavior

A high-fat diet (HFD) causes inflammation with an increase in microglial activity in the hypothalamic arcuate nucleus (ARC) and ventral tegmental area (VTA), resulting in insulin resistance in both regions. This leads to a deterioration in glucose and energy metabolism. The effect of voluntary exercise on HFD-induced inflammation in the central nervous system (CNS) remains unclear. To clarify the effects of voluntary exercise on the CNS, 8-week-old male C57BL6 mice were fed a chow diet (CHD) or HFD for 4 weeks; each group was further divided into running exercise (EX+) on a wheel and no exercise (EX-) groups. The expression of the inflammatory cytokine, tumor necrosis factor alpha (TNFα), in the ARC and VTA was significantly increased in the HFD/EX- group, with an increase of microglial activity noted, compared to the CHD/EX- group. The expression of TNFα was significantly suppressed, with a decrease of microglial activity, in the HFD/EX+ compared to HFD/EX- group. Insulin resistance in the ARC and VTA was improved with the suppression of TNFα expression. The HFD/EX- group showed significant weight gain and impaired glucose metabolism compared to the CHD/EX- group. The HFD/EX+ group showed an improvement in glucose and energy metabolism compared to the HFD/EX- group. In addition, voluntary wheel running suppressed HFD-induced inflammation in the ARC, with a decrease in microglial activity observed independently of weight changes. Our data suggest that voluntary exercise prevents obesity and improves glucose metabolism by suppressing inflammation in the ARC and VTA under HFD conditions.

DOI： 10.1016/j.physbeh.2024.114703

Thyroid autoantibodies at baseline predict longer survival in non-small cell lung cancer patients treated with anti-programmed cell death-1 blockade: a prospective study 査読有り

Okuji, T; Iwama, S; Kobayashi, T; Yasuda, Y; Ito, M; Yamagami, A; Ando, M; Hase, T; Shibata, H; Hatta, T; Zhou, X; Onoue, T; Kawaguchi, Y; Miyata, T; Sugiyama, M; Hagiwara, D; Suga, H; Banno, R; Ando, Y; Hashimoto, N; Arima, H

NAGOYA JOURNAL OF MEDICAL SCIENCE 86 巻 ( 3 ) 頁： 452 - 463 2024年8月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nagoya Journal of Medical Science

The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had ≥50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1.

DOI： 10.18999/nagjms.86.3.452

Hyperthyroidism Due to Functioning Metastatic Bone Lesions of Follicular Thyroid Carcinoma Treated With Lenvatinib. 査読有り

Kobayashi T, Iwama S, Suzuki K, Arima H

JCEM case reports 2 巻 ( 7 ) 頁： luae139 2024年7月

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 査読有り国際誌

Kobayashi, T; Iwama, S; Yamagami, A; Izuchi, T; Suzuki, K; Otake, K; Yasuda, Y; Ando, M; Onoue, T; Miyata, T; Sugiyama, M; Hagiwara, D; Suga, H; Banno, R; Hase, T; Nishio, N; Mori, S; Shimokata, T; Sano, T; Niimi, K; Yoshikawa, N; Akamatsu, S; Ando, Y; Akiyama, M; Sone, M; Ishii, M; Arima, H

CANCER IMMUNOLOGY IMMUNOTHERAPY 73 巻 ( 8 ) 頁： 146 - 146 2024年6月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Immunology, Immunotherapy

Background: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI]. Methods: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit. Results: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026]. Conclusions: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

DOI： 10.1007/s00262-024-03733-2

A case of hypophysitis after COVID-19 vaccination with a detection of anti-pituitary antibody, with review of literature 査読有り

Kyo, C; Kobayashi, T; Iwama, S; Kosugi, R; Sawabe, F; Hayafusa, R; Sakai, Y; Ogawa, T; Kotani, M; Inoue, T; Arima, H; Ariyasu, H

ENDOCRINE JOURNAL 71 巻 ( 8 ) 頁： 799 - 807 2024年5月

Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells. 査読有り

Miwata T, Suga H, Mitsumoto K, Zhang J, Hamada Y, Sakakibara M, Soen M, Ozaki H, Asano T, Miyata T, Kawaguchi Y, Yasuda Y, Kobayashi T, Sugiyama M, Onoue T, Hagiwara D, Iwama S, Oyadomari S, Arima H

Peptides 173 巻頁： 171151 - 171151 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Peptides

Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.

DOI： 10.1016/j.peptides.2024.171151

Rapidly progressive interstitial lung disease with positive anti-MDA5 antibody as an immune-related complication of nivolumab: A case report 査読有り

Kato S, Sakamoto K, Sato T, Kobayashi T, Shindo Y, Morise M, Iwama S, Arima H, Ishii M.

Respir Investig 62 巻 ( 2 ) 頁： 313 - 316 2024年3月

Effects of Digitization of Self-Monitoring of Blood Glucose Records Using a Mobile App and the Cloud System on Outpatient Management of Diabetes: Single-Armed Prospective Study. 査読有り国際誌

Handa T, Onoue T, Kobayashi T, Maeda R, Mizutani K, Yamagami A, Kinoshita T, Yasuda Y, Iwama S, Miyata T, Sugiyama M, Takagi H, Hagiwara D, Suga H, Banno R, Azuma Y, Kasai T, Yoshioka S, Kuwatsuka Y, Arima H

JMIR diabetes 9 巻 ( 1 ) 頁： e48019 2024年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JMIR Diabetes

Background: In recent years, technologies promoting the digitization of self-monitoring of blood glucose (SMBG) records including app-cloud cooperation systems have emerged. Studies combining these technological interventions with support from remote health care professionals have reported improvements in glycemic control. Objective: To assess the use of an app-cloud cooperation system linked with SMBG devices in clinical settings, we evaluated its effects on outpatient management of diabetes without remote health care professional support. Methods: In this multicenter, open-label, and single-armed prospective study, 48 patients with diabetes (including type 1 and type 2) at 3 hospitals in Japan treated with insulin or glucagon-like peptide 1 receptor agonists and performing SMBG used the app-cloud cooperation system for 24 weeks. The SMBG data were automatically uploaded to the cloud via the app. The patients could check their data, and their attending physicians reviewed the data through the cloud prior to the patients’ regular visits. The primary outcome was changes in glycated hemoglobin (HbA1c) levels. Results: Although HbA1c levels did not significantly change in all patients, the frequency of daily SMBG following applying the system was significantly increased before induction at 12 (0.60 per day, 95% CI 0.19-1.00; P=.002) and 24 weeks (0.43 per day, 95% CI 0.02-0.84; P=.04). In the subset of 21 patients whose antidiabetic medication had not been adjusted during the intervention period, a decrease in HbA1c level was observed at 12 weeks (P=.02); however, this significant change disappeared at 24 weeks (P=.49). The Diabetes Treatment Satisfaction Questionnaire total score and “Q4: convenience” and “Q5: flexibility” scores significantly improved after using the system (all P<.05), and 72% (33/46) patients and 76% (35/46) physicians reported that the app-cloud cooperation system helped them adjust insulin doses. Conclusions: The digitization of SMBG records and sharing of the data by patients and attending physicians during face-to-face visits improved self-management in patients with diabetes.

DOI： 10.2196/48019

Clinical characteristics and potential biomarkers of thyroid and pituitary immune-related adverse events 招待有り査読有り

Kobayashi, T; Iwama, S; Arima, H

ENDOCRINE JOURNAL 71 巻 ( 1 ) 頁： 23 - 29 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Endocrine Journal

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs) in several organs including endocrine glands. Among endocrine irAEs, thyroid and pituitary irAEs are frequently observed, followed by primary adrenal insufficiency, insulin-dependent diabetes mellitus, and hypoparathyroidism. These conditions could lead to life-threatening consequences, such as adrenal crisis and diabetic ketoacidosis. On the other hand, several types of irAEs including thyroid and pituitary irAEs are reported to be associated with better overall survival. Therefore, it is important to understand and manage endocrine irAEs, which differ depending on the ICI regimen used. In this review, we describe the clinical features, potential biomarkers, management strategies, and possible mechanisms of thyroid and pituitary irAEs.

DOI： 10.1507/endocrj.EJ23-0524

Changes in TgAb and TPOAb titers are greater in thyrotoxicosis than isolated hypothyroidism induced by PD-1 blockade 査読有り

Yamagami, A; Iwama, S; Kobayashi, T; Zhou, X; Yasuda, Y; Okuji, T; Ito, M; Izuchi, T; Ando, M; Onoue, T; Miyata, T; Sugiyama, M; Hagiwara, D; Suga, H; Banno, R; Arima, H

ENDOCRINE JOURNAL 71 巻 ( 5 ) 頁： 515 - 526 2024年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Endocrine Journal

Anti-thyroglobulin antibodies (TgAb) and/or anti-thyroid peroxidase antibodies (TPOAb) positivity at baseline is a risk marker for thyroid immune-related adverse events (thyroid-irAEs) in anti-programmed cell death-1 antibody (PD-1-Ab) treatment; however, it is unknown if TgAb and TPOAb titers are associated with clinical characteristics of thyroid-irAEs. Among 586 patients treated with PD-1-Ab at Nagoya University Hospital between 2 November 2015 and 30 September 2021, 57 patients developed thyroid-irAEs (thyrotoxicosis [n = 38]; hypothyroidism without prior thyrotoxicosis {isolated hypothyroidism} [n = 19]) in whom thyroid function, and TgAb and TPOAb titers were determined at baseline and at the onset. The changes in TgAb (median, 54.8 vs. 0.2 IU/mL; p = 0.002) and TPOAb titers (31.6 vs. 0 IU/mL; p = 0.032) from baseline to onset of developing thyroid-irAEs were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism. Higher TgAb and TPOAb titers, and the TgAb titer at baseline were associated with an earlier onset of thyrotoxicosis and higher peak free thyroxine levels, respectively. Twenty-eight patients who developed hypothyroidism after thyrotoxicosis had higher TgAb (54.5 vs. 10.7 IU/mL; p = 0.011) and TPOAb titers at baseline (46.1 vs. 9.0 IU/mL; p < 0.001) and greater changes in TgAb (61.7 vs. 7.8 IU/mL; p = 0.025) and TPOAb titers (52.8 vs. –0.8 IU/mL; p < 0.001) than patients who did not develop hypothyroidism. The TgAb titer at baseline and changes in the TgAb and TPOAb titers were greater in patients with thyrotoxicosis than patients with isolated hypothyroidism, suggesting that the magnitude of the thyroid autoimmune response reflects the clinical types of thyroid-irAEs.

DOI： 10.1507/endocrj.EJ23-0480

Improved glycemic control after the use of flash glucose monitoring accompanied by improved treatment satisfaction in patients with non-insulin-treated type 2 diabetes: A post-hoc analysis of a randomized controlled trial 査読有り国際誌

Hayase, A; Onoue, T; Kobayashi, T; Wada, E; Handa, T; Kinoshita, T; Yamagami, A; Yasuda, Y; Iwama, S; Kawaguchi, Y; Miyata, T; Sugiyama, M; Takagi, H; Hagiwara, D; Suga, H; Banno, R; Kuwatsuka, Y; Ando, M; Goto, M; Arima, H

PRIMARY CARE DIABETES 17 巻 ( 6 ) 頁： 575 - 580 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Primary Care Diabetes

Aims: In our previously reported randomized controlled trial in patients with noninsulin-treated type 2 diabetes, the use of flash glucose monitoring (FGM) improved glycated hemoglobin (HbA1c), and the improvement was sustained after the cessation of glucose monitoring. In this post-hoc analysis, we examined data from our trial to identify the factors that influenced FGM efficacy. Methods: We analyzed data for 48 of 49 participants of the FGM group who completed the trial to clarify the changes in various parameters and factors related to HbA1c improvement with the use of FGM. Results: Analyses of the FGM data during the 12-week FGM provision period showed that the weekly mean blood glucose levels considerably decreased as early as at 1 week compared with the baseline values, and this decline continued for 12 weeks. An enhancement in the Diabetes Treatment Satisfaction Questionnaire regarding “willingness to continue the current treatment” score was significantly associated with the improvement in HbA1c at 12 (p = 0.009) and 24 weeks (p = 0.012). Conclusions: Glycemic control was improved soon after FGM initiation, accompanied by improved satisfaction with continuation of the current treatment in patients with noninsulin-treated type 2 diabetes.

DOI： 10.1016/j.pcd.2023.09.009

Risk of Thyroid Dysfunction in PD-1 Blockade Is Stratified by the Pattern of TgAb and TPOAb Positivity at Baseline 査読有り

Zhou, X; Iwama, S; Kobayashi, T; Ando, M; Arima, H

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 108 巻 ( 10 ) 頁： E1056 - E1062 2023年9月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：The Journal of clinical endocrinology and metabolism

CONTEXT: Positive antithyroglobulin (TgAb) and/or antithyroid peroxidase antibodies (TPOAb) at baseline indicate a high risk of thyroid immune-related adverse events (irAEs) induced by antiprogrammed cell death-1 antibodies (anti-PD-1-Ab). However, whether the positivity patterns of both antibodies are associated with the risk of thyroid irAEs is unknown. OBJECTIVE: The aim of the present study was to clarify the association of the pattern of TgAb and TPOAb positivity at baseline with the risk of thyroid irAEs induced by anti-PD-1-Ab. METHODS: Patients (n = 516) were evaluated for TgAb and TPOAb at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after initiating anti-PD-1-Ab. RESULTS: Fifty-one (9.9%) patients developed thyroid irAEs (thyrotoxicosis in 34, hypothyroidism without prior thyrotoxicosis in 17). Twenty-five patients subsequently developed hypothyroidism following thyrotoxicosis. The cumulative incidence of thyroid irAEs differed among 4 groups classified by the presence of TgAb/TPOAb at baseline (group 1: TgAb-(-)/TPOAb-(-), 4.6% [19/415]; group 2: TgAb-(-)/TPOAb-(+), 15.8% [9/57]; group 3: TgAb-(+)/TPOAb-(-), 42.1% [8/19]; group 4: TgAb-(+)/TPOAb-(+), 60.0% [15/25]) as follows: groups 1 vs 2-4 (P ≤ .001) and groups 2 vs 3 (P = .008) and 4 (P < .001). There were different incidences of thyrotoxicosis (groups 1-4, 3.1%, 5.3%, 31.6%, 48.0%, respectively; P < .001) in groups 1 vs 3 and 4, and groups 2 vs 3 and 4, and of hypothyroidism (groups 1-4: 2.9%, 15.8%, 31.6%, 60.0%, respectively; P < .001) in groups 1 vs 2 to 4, and groups 2 vs 4. CONCLUSION: The risk of thyroid irAEs was affected by the pattern of TgAb and TPOAb positivity at baseline; there were high risks of thyrotoxicosis in patients with TgAb-(+) and of hypothyroidism in patients with TgAb-(+) and those with TPOAb-(+).

DOI： 10.1210/clinem/dgad231

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