Faculty Profiles - ARIMA, Hiroshi

Utility of albumin-adjusted calcium and calcium-phosphorus difference in screening for primary hyperparathyroidism Open Access

Okumura, A; Bando, T; Ashida, R; Kuno, M; Tamaki, N; Mizuguchi, T; Uchida, I; Arima, H

BMC ENDOCRINE DISORDERS Vol. 26 ( 1 ) 2026.4

In vitro differentiation of the hypothalamic KNDy neuron, a master regulator for reproduction, from mouse embryonic stem cells (Vol 24, 40, 2025) Open Access

Miyake, N; Suga, H; Osuka, S; Seki, T; Sonehara, R; Muraoka, A; Nakamura, T; Bayasula; Miwata, T; Soen, M; Sakakibara, M; Go, S; Hasegawa, S; Inoue, N; Uenoyama, Y; Tsukamura, H; Arima, H; Kajiyama, H

REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY Vol. 24 ( 1 ) 2026.4

Concurrent Pituitary and Thyroid Immune-Related Adverse Events after Immune Checkpoint Inhibitors Associated with HLA-DR15-Related Haplotypes. International journal Open Access

Tomoko Kobayashi, Shintaro Iwama, Eri Sugiyama, Shohei Koyama, Tetsushi Izuchi, Koji Suzuki, Takanori Murase, Masahiko Ando, Hidefumi Inaba, Hiroki Izumi, Koichi Goto, Tomoko Handa, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Yoshiki Akatsuka, Hiroyoshi Nishikawa, Hiroshi Arima

Cancer immunology research Vol. 14 ( 4 ) page： 599 - 607 2026.4

Language：English Publishing type：Research paper (scientific journal)

Some patients undergoing immune checkpoint blockade treatment develop immune-related adverse events (irAE) affecting multiple organs, but whether pituitary and thyroid dysfunction is prone to co-occur is unclear. A total of 1,014 patients treated at Nagoya University Hospital were prospectively assessed for pituitary and thyroid function, and human leukocyte antigens (HLA) were analyzed in patients with pituitary and/or thyroid irAEs. Pituitary irAE and thyroid irAE developed in 68 and 128 patients, respectively. The incidence of thyroid irAE was significantly higher in patients who developed pituitary irAE compared with those who did not [21/68 (30.9%) vs. 107/946 (11.3%), P < 0.001], and the difference remained significant with tumor type and therapeutic agents used as stratified factors (Cochran-Mantel-Haenszel test, P = 0.001). The frequencies of HLA-DRB1*15:01 (12.5% vs. 7.6%, P = 0.049) and DRB1*15:02 (16.9% vs. 10.6%, P = 0.025) were significantly higher in patients with pituitary irAE compared with those in a database containing Japanese subjects. The frequency of the DRB1*15:01-associated haplotype (DRB1*15:01-DQB1*06:02-DPB1*02:01) was significantly higher in patients who developed both pituitary and thyroid irAEs compared with the control (14.3% vs. 3.1%, P = 0.002), and the DRB1*15:02-associated haplotype (DRB1*15:02-DQB1*06:01-DPB1*09:01) frequency was significantly higher in patients who developed pituitary irAE but not thyroid irAE compared with the control (18.1% vs. 8.9%, P = 0.006); both findings were confirmed in the validation cohort comprising 92 patients with pituitary irAE from seven hospitals. In conclusion, pituitary and thyroid irAEs are prone to co-occur, and HLA-DR15-associated haplotypes are related to this co-occurrence.

DOI： 10.1158/2326-6066.CIR-25-0693

In vitro differentiation of the hypothalamic KNDy neuron, a master regulator for reproduction, from mouse embryonic stem cells Open Access

Pituitary Regenerative Medicine Open Access

Suga, H; Arima, H

INTERNAL MEDICINE 2026.3

REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY Vol. 24 ( 1 ) 2026.2

Defining a serum cortisol cutoff level post-CRH stimulation for diagnosing ACTH deficiency: A retrospective study validated by a nationwide registry Open Access

Izuchi, T; Iwama, S; Yamagami, A; Kobayashi, T; Suzuki, K; Murase, T; Ando, M; Murasawa, S; Mukai, K; Takagi, H; Fukuoka, H; Handa, T; Onoue, T; Miyata, T; Sugiyama, M; Hagiwara, D; Suga, H; Banno, R; Tahara, S; Nishiyama, M; Kageyama, K; Otsuki, M; Arima, H

FRONTIERS IN ENDOCRINOLOGY Vol. 17 page： 1741709 2026.2

The time of the hypertonic saline infusion test for the diagnosis of AVP deficiency can be shortened with LC-MS/MS. International journal Open Access

Tomoko Handa, Daisuke Hagiwara, Ryutaro Maeda, Takashi Miyata, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Yachiyo Kuwatsuka, Hiroshi Arima

The Journal of clinical endocrinology and metabolism Vol. 111 ( 2 ) page： e382 - e389 2026.2

Language：English Publishing type：Research paper (scientific journal)

CONTEXT: In clinical practice, plasma arginine vasopressin (AVP) concentrations have been measured with a radioimmunoassay (RIA). However, RIAs have limitations, such as long turnaround time, use of radioisotopes, and restricted antibody availability. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) offers a promising alternative, eliminating the need for radioisotopes and antibodies while providing faster results. OBJECTIVE: This study aimed to assess the usefulness of LC-MS/MS for measuring plasma AVP concentrations in diagnosing AVP deficiency (AVP-D). METHODS: We included 16 patients with AVP-D and 28 controls. All participants underwent a hypertonic saline infusion test (HST), during which plasma AVP concentrations were measured using RIA and LC-MS/MS. Regression coefficients (gradients) for serum sodium versus plasma AVP concentrations were evaluated at 90 and 120 min, and receiver-operating characteristic (ROC) analyses were performed based on these regression coefficients. RESULTS: The area under the ROC curve at 90 min was 0.97 (95% CI: 0.83-1.00) and 0.93 (95% CI: 0.80-0.98) for LC-MS/MS and RIA, respectively. A regression gradient cut-off with optimal values distinguished AVP-D from controls with a sensitivity of 100% in LC-MS/MS and RIA, whereas the specificity was 96% and 81% with LC-MS/MS and RIA, respectively. Sensitivity or specificity did not differ in 120 min between the two methods. CONCLUSION: LC-MS/MS demonstrated superior diagnostic accuracy for AVP-D at 90 min of HST, indicating that the HST time can be shortened from 120 to 90 min by measuring AVP with LC-MS/MS.

DOI： 10.1210/clinem/dgaf432

Consensus on the Diagnosis of Cushing's Disease: A Collaborative Statement from the Korean Endocrine Society and Japan Endocrine Society Open Access

Lee, J; Fukuoka, H; Park, SS; Hong, AR; Kim, JH; Chin, SO; Baek, HS; Lim, DJ; Kageyama, K; Nishiyama, M; Tahara, S; Oyama, K; Sugawara, A; Yamashita, M; Inoshita, N; Arima, H; Kim, BJ; Chung, YS; Yoo, SJ; Otsuki, M; Kim, MK

ENDOCRINOLOGY AND METABOLISM Vol. 41 ( 1 ) page： 1 - 13 2026.2

Increased HbA1c relative to actual glycemic control in patients treated with sodium-glucose cotransporter 2 inhibitors. Open Access

Keigo Mizutani, Eita Uenishi, Takeshi Onoue, Ryutaro Maeda, Koji Suzuki, Tomoko Handa, Tomoko Kobayashi, Shintaro Iwama, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Masaki Okazaki, Atsushi Hashizume, Hiroshi Arima

Journal of diabetes investigation Vol. 17 ( 1 ) page： 34 - 41 2026.1

Language：English Publishing type：Research paper (scientific journal)

AIMS/INTRODUCTION: Among patients with diabetes receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors, HbA1c levels are higher than glycated albumin levels. This study therefore aimed to evaluate the discrepancy between HbA1c and glucose management indicator (GMI), an index of glucose management derived from continuous glucose monitoring, in this population. MATERIALS AND METHODS: This multicenter retrospective cohort study included patients with diabetes in whom HbA1c and GMI were simultaneously measured at two Japanese institutions. Data were collected when HbA1c levels had stabilized for at least 6 months after the administration of an oral hypoglycemic agent. The primary outcome was the discrepancy between HbA1c and GMI among patients receiving SGLT2 inhibitors and those receiving other oral hypoglycemic agents. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding factors. RESULTS: In total, 136 patients were included; of these, 109 and 27 were included in the SGLT2 inhibitor group and control group, respectively. After IPTW adjustment, the discrepancy between HbA1c and GMI (HbA1c-GMI) was significantly higher in the SGLT2 inhibitor group than in the control group (β = 0.42; 95% confidence interval 0.14-0.70; P = 0.003). CONCLUSIONS: Patients receiving SGLT2 inhibitors may have increased HbA1c relative to their actual glycemic control.

DOI： 10.1111/jdi.70191

Consensus on the diagnosis of Cushing's disease: a collaborative statement from the Korean Endocrine Society and Japan Endocrine Society Open Access

Lee, J; Fukuoka, H; Park, SS; Hong, AR; Kim, JH; Chin, SO; Baek, HS; Lim, DJ; Kageyama, K; Nishiyama, M; Tahara, S; Oyama, KI; Sugawara, A; Yamashita, M; Inoshita, N; Arima, H; Kim, BJ; Chung, YS; Yoo, SJ; Otsuki, M; Kim, MK

ENDOCRINE JOURNAL Vol. 73 ( 2 ) page： 355 - 366 2026

Diagnostic criteria for acquired hypothalamic obesity-international expert guidance document Open Access

Müller, HL; Tanaka, T; Hasegawa, T; Isojima, T; Mori, J; Kurosaki, M; Nishioka, H; Choi, HJ; Hong, AR; Kim, JH; Arima, H

ENDOCRINE JOURNAL Vol. 73 ( 2 ) page： 341 - 353 2026

Increased risk of hyperthyroidism induced by immune checkpoint inhibitors in patients with existing or prior Graves' disease: a nested prospective cohort study with propensity score matching. International journal Open Access

Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Takanori Murase, Masahiko Ando, Tomoko Handa, Takeshi Onoue, Takashi Miyata, Mariko Sugiyama, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Hiroshi Arima, Shintaro Iwama

Frontiers in endocrinology Vol. 16 page： 1701500 - 1701500 2025.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Thyroid dysfunction induced by immune checkpoint inhibitors (ICIs) commonly manifests as destructive thyroiditis and hypothyroidism, while hyperthyroidism (Graves' disease) is rare. However, the clinical characteristics of thyroid dysfunction in patients with existing or prior Graves' disease treated with ICIs remain unclear. METHODS: A case-control study was performed using a prospective cohort of patients treated with ICIs between November 2015 and January 2024. At baseline, cases had Graves' disease without overt thyroid dysfunction or prior Graves' disease and were matched 1:5 with controls by age, gender, antithyroid antibody status at baseline, and ICI type. The incidence of thyroid dysfunction induced by ICIs was compared between cases and controls. The incidence of hyperthyroidism was compared with the exacerbation rate in ICI-untreated outpatients with Graves' disease who were in remission or had no overt thyroid dysfunction for ≥1 year without changes in low-dose antithyroid medication. RESULTS: Nineteen patients (13 in remission and 6 receiving thiamazole at baseline) were included and matched with 95 controls. During follow-up, 5 cases negative for thyroid-stimulating hormone receptor antibody (TRAb) at baseline developed thyrotoxicosis: 3 were TRAb-positive (2 with increased uptake on thyroid scintigraphy) suggesting hyperthyroidism, and 2 had destructive thyroiditis (TRAb-negative). The incidence of hyperthyroidism was significantly higher in cases than in controls (3/19 [15.8%] vs 0/95 [0%], p < 0.05), whereas the incidence of destructive thyroiditis (2/19 [10.5%] vs. 15/95 [15.8%], p = 0.734) or isolated hypothyroidism (0/19 [0%] vs. 13/95 [13.7%], p = 0.121) did not differ between groups. The incidence of hyperthyroidism was also higher in cases than in outpatients with ICI-unrelated Graves' disease (3/19 [15.8%] vs 10/269 [3.7%], respectively; p < 0.05). CONCLUSION: Patients with existing or prior Graves' disease have an increased risk of hyperthyroidism following ICI treatment, highlighting their need for careful differential diagnosis of thyrotoxicosis.

DOI： 10.3389/fendo.2025.1701500

Efficacy of luseogliflozin for renal function preservation in patients with type 2 diabetes mellitus and impaired renal function: A randomized open-label clinical trial (RESOLUTION study) Open Access

Kitada, M; Toyoda, M; Sekine, O; Suzuki, D; Okada, Y; Morita, Y; Nishimura, H; Satoh, H; Kamiya, H; Takamura, T; Isono, M; Onoue, T; Arima, H; Tanaka, K; Miyamoto, M; Omura, Y; Yabe, D; Kato, T; Asano, A; Wakasa, Y; Miyamoto, S; Kume, S; Ito, T; Araki, S; Nakagawa, A; RESOLUTION Study Investigators

JOURNAL OF DIABETES INVESTIGATION Vol. 16 ( 12 ) page： 2160 - 2172 2025.12

Phagophores originate from endoplasmic reticulum membranes in vasopressin neurons in a mouse model of familial neurohypophysial diabetes insipidus Open Access

Takashi Miyata, Daisuke Hagiwara, Ryosei Ashida, Satoshi Naito, Yohei Kawaguchi, Tomoko Handa, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Shintaro Iwama, Hidetaka Suga, Ryoichi Banno, Mami Matsumoto, Hidetoshi Urakubo, Nobuhiko Ohno, Hiroshi Arima

Cell and Tissue Research Vol. 402 ( 2 ) page： 139 - 144 2025.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Familial neurohypophysial diabetes insipidus (FNDI) is an autosomal dominant disorder caused by mutations in the arginine vasopressin (AVP) gene. In AVP neurons in a mouse model of FNDI, aggregates of mutant AVP precursors accumulate within a specific compartment of the endoplasmic reticulum (ER). However, as FNDI mice aged, or were exposed to repeated water deprivation, the ER lumen dilated and mutant aggregates dispersed throughout the ER. Meanwhile, autophagic isolation membranes, known as phagophores, emerged to envelop ER containing these aggregates, indicating induction of ER-phagy. Previous in vitro studies showed that phagophores originate from ER membranes, but the structural relationship between phagophores and the ER membrane in vivo remains unknown. In this study, we used serial block-face scanning electron microscopy to investigate the structural relationship between phagophores, ER membranes, and protein aggregates within dilated ER of AVP neurons from FNDI mice subjected to intermittent water deprivation for 4 weeks. Three-dimensional analysis revealed that phagophores enveloped aggregates located within the dilated ER. Serial imaging further demonstrated a physical connection between these phagophores and intact ER membranes. This study provides the first in vivo evidence of the structural continuity between phagophores and the ER membrane in AVP neurons in a mouse model of FNDI.

DOI： 10.1007/s00441-025-04013-w