九州大学 研究者情報
論文一覧
松田 やよい(まつだ やよい) データ更新日:2023.11.06

助教 /  九州大学病院 内分泌代謝・糖尿病内科 九州大学大学院医学研究院 病態制御内科学


原著論文
1. Hiroshi Nakao, Maki Yokomoto-Umakoshi, Kohta Nakatani, Hironobu Umakoshi, Masatoshi Ogata, Tazuru Fukumoto, Hiroki Kaneko, Norifusa Iwahashi, Masamichi Fujita, Tatsuki Ogasawara, Yayoi Matsuda, Ryuichi Sakamoto, Yoshihiro Izumi, Takeshi Bamba, Yoshihiro Ogawa, Adrenal steroid metabolites and bone status in patients with adrenal incidentalomas and hypercortisolism, eBioMedicine, 10.1016/j.ebiom.2023.104733, 104733-104733, 2023.08.
2. Hiroki Kaneko, Hironobu Umakoshi, Tazuru Fukumoto, Norio Wada, Takamasa Ichijo, Shohei Sakamoto, Tetsuhiro Watanabe, Yuki Ishihara, Tetsuya Tagami, Masatoshi Ogata, Norifusa Iwahashi, Maki Yokomoto-Umakoshi, Yayoi Matsuda, Ryuichi Sakamoto, Yoshihiro Ogawa, Do multiple types of confirmatory tests improve performance in predicting subtypes of primary aldosteronism?, Clinical endocrinology, 2022.11.
3. Chieko Yano, Maki Yokomoto-Umakoshi, Masamichi Fujita, Hironobu Umakoshi, Seiichi Yano, Norifusa Iwahashi, Shunsuke Katsuhara, Hiroki Kaneko, Masatoshi Ogata, Tazuru Fukumoto, Eriko Terada, Yayoi Matsuda, Ryuichi Sakamoto, Yoshihiro Ogawa, Coexistence of bone and vascular disturbances in patients with endogenous glucocorticoid excess., Bone reports, 10.1016/j.bonr.2022.101610, 17, 101610-101610, 2022.12, Purpose: Bone and vascular diseases are considered to share pathogenic mechanisms. Excess glucocorticoids, key regulators of cardiovascular and metabolic homeostasis, may promote both diseases simultaneously. We used endogenous Cushing's syndrome (CS) to investigate whether glucocorticoid excess underlies coexisting bone and vascular diseases. Methods: We included 194 patients with adrenal tumors (ATs): autonomous cortisol secretion (ACS, n = 97) and non-functional AT (n = 97). ACS was further classified into overt CS (n = 17) and subclinical CS (SCS, n = 80). Arterial stiffness was defined as a brachial-ankle pulse wave velocity (baPWV) ≥ 1800 cm/s. Results: Patients with ACS had higher coexistence rates of vertebral fracture and arterial stiffness (23 % vs. 2 %; p 
4. Shunsuke Katsuhara, Maki Yokomoto-Umakoshi, Hironobu Umakoshi, Yayoi Matsuda, Norifusa Iwahashi, Hiroki Kaneko, Masatoshi Ogata, Tazuru Fukumoto, Eriko Terada, Ryuichi Sakamoto, Yoshihiro Ogawa, Impact of Cortisol on Reduction in Muscle Strength and Mass: A Mendelian Randomization Study., The Journal of clinical endocrinology and metabolism, 2022.05.
5. Maki Yokomoto-Umakoshi, Hironobu Umakoshi, Norifusa Iwahashi, Yayoi Matsuda, Hiroki Kaneko, Masatoshi Ogata, Tazuru Fukumoto, Eriko Terada, Yui Nakano, Ryuichi Sakamoto, Yoshihiro Ogawa, Protective Role of DHEAS in Age-related Changes in Bone Mass and Fracture Risk: A Mendelian Randomization Study., The Journal of clinical endocrinology and metabolism, 2021.11.
6. 梶野 美保, 淀川 千穂, 坂本 竜一, 松田 やよい, 大隈 俊明, 佐藤 直市, 勝田 仁, 小川 佳宏, 手術予定患者に対する糖尿病治療介入必要度トリアージの試み, 糖尿病, 66, 5, 449-449, 2023.05.
7. Hiroki Kaneko, Hironobu Umakoshi, Masatoshi Ogata, Norio Wada, Norifusa Iwahashi, Tazuru Fukumoto, Maki Yokomoto-Umakoshi, Yui Nakano, Yayoi Matsuda, Takashi Miyazawa, Ryuichi Sakamoto, Yoshihiro Ogawa, Machine learning based models for prediction of subtype diagnosis of primary aldosteronism using blood test., Scientific reports, 10.1038/s41598-021-88712-8, 11, 1, 9140-9140, 2021.05, Primary aldosteronism (PA) is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who should be referred to specialized centers. The aim of this retrospective cross-sectional study was to develop a predictive model for subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Overall, 91 patients with unilateral and 138 patients with bilateral PA were randomly assigned to the training and test cohorts. Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop predictive models from 21 clinical variables. The accuracy and the area under the receiver operating characteristic curve (AUC) for predicting of subtype diagnosis of PA in the test cohort were compared among the optimized classifiers. Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium, plasma aldosterone, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF (accuracy: 85.1%). Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice..
8. Nozomi Kawata, Hirokazu Takahashi, Shinji Iwane, Kanako Inoue, Motoyasu Kojima, Michiko Kohno, Kenichi Tanaka, Hitoe Mori, Hiroshi Isoda, Satoshi Oeda, Yayoi Matsuda, Yoshiaki Egashira, Jyunichi Nojiri, Hiroyuki Irie, Yuichiro Eguchi, Keizo Anzai, FIB-4 index-based surveillance for advanced liver fibrosis in diabetes patients., Diabetology international, 10.1007/s13340-020-00453-7, 12, 1, 118-125, 2021.01, Liver fibrosis is associated with lifestyle-related diseases, including diabetes. The identification of diabetic patients with severe liver fibrosis is important, but a simple and reliable diagnostic procedure remains to be determined. We conducted an observational study to evaluate the performance of a FIB-4 index-based screening strategy for the diagnosis of advanced liver fibrosis in patients with diabetes or prediabetes. Two hundred and forty-two patients underwent abdominal imaging in our Study. According to the abdominal imaging findings, fatty liver, liver cirrhosis, and hepatocellular carcinoma were defined, and their association with FIB-4 index evaluated. The prevalences of liver cirrhosis and hepatocellular carcinoma in patients with a high (≥ 2.67; liver cirrhosis: 42.9%, hepatocellular carcinoma: 14.3%) FIB-4 index were significantly higher than in those with an intermediate (1.3 ≤ FIB-4 
9. Tazuru Fukumoto, Hironobu Umakoshi, Masatoshi Ogata, Maki Yokomoto-Umakoshi, Yayoi Matsuda, Misato Motoya, Hiromi Nagata, Yui Nakano, Norifusa Iwahashi, Hiroki Kaneko, Norio Wada, Takashi Miyazawa, Ryuichi Sakamoto, Yoshihiro Ogawa, Significance of Discordant Results Between Confirmatory Tests in Diagnosis of Primary Aldosteronism., The Journal of clinical endocrinology and metabolism, 10.1210/clinem/dgaa812, 106, 2, e866-e874, 2021.01, CONTEXT: Current clinical guidelines recommend confirmation of a positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results. OBJECTIVE: The aim of the present study was to explore the role of 2 confirmatory tests in subtype diagnosis of PA. DESIGN AND SETTING: A retrospective cross-sectional study was conducted at two referral centers. PARTICIPANTS AND METHODS: We identified 360 hypertensive patients who underwent both a captopril challenge test (CCT) and a saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS). MAIN OUTCOME MEASURE: The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests was measured. RESULTS: Of patients studied, 127 were positive for both CCT and SIT (double-positive), whereas 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs 72/127 [56.7%], P 
10. Motoyasu Kojima, Hirokazu Takahashi, Takuya Kuwashiro, Kenichi Tanaka, Hitoe Mori, Iwata Ozaki, Yoichiro Kitajima, Yayoi Matsuda, Kenji Ashida, Yuichiro Eguchi, Keizo Anzai, Glucagon-Like Peptide-1 Receptor Agonist Prevented the Progression of Hepatocellular Carcinoma in a Mouse Model of Nonalcoholic Steatohepatitis., International journal of molecular sciences, 10.3390/ijms21165722, 21, 16, 2020.08, Glucagon-like peptide-1 (GLP-1) receptor agonists are used to treat diabetes, but their effects on nonalcoholic steatohepatitis (NASH) and the development of hepatocellular carcinoma (HCC) remain unclear. In this study, mice with streptozotocin- and high-fat diet-induced diabetes and NASH were subcutaneously treated with liraglutide or saline (control) for 14 weeks. Glycemic control, hepatocarcinogenesis, and liver histology were compared between the groups. Fasting blood glucose levels were significantly lower in the liraglutide group than in the control group (210.0 ± 17.3 mg/dL vs. 601.8 ± 123.6 mg/dL), and fasting insulin levels were significantly increased by liraglutide (0.18 ± 0.06 ng/mL vs. 0.09 ± 0.03 ng/mL). Liraglutide completely suppressed hepatocarcinogenesis, whereas HCC was observed in all control mice (average tumor count, 5.5 ± 3.87; average tumor size, 8.1 ± 5.0 mm). Liraglutide significantly ameliorated steatosis, inflammation, and hepatocyte ballooning of non-tumorous lesions in the liver compared with the control findings, and insulin-positive β-cells were observed in the pancreas in liraglutide-treated mice but not in control mice. In conclusion, liraglutide ameliorated NASH and suppressed hepatocarcinogenesis in diabetic mice. GLP-1 receptor agonists can be used to improve the hepatic outcome of diabetes..
11. Maki Yokomoto-Umakoshi, Hironobu Umakoshi, Ryuichi Sakamoto, Tazuru Fukumoto, Masatoshi Ogata, Yui Nakano, Norifusa Iwahashi, Hiroki Kaneko, Noriko Mizoguchi, Akiko Hattori, Takashi Miyazawa, Yayoi Matsuda, Hisaya Kawate, Yoshihiro Ogawa, Role of deteriorated bone quality in the development of osteoporosis in pheochromocytoma and paraganglioma., Bone, 10.1016/j.bone.2020.115607, 142, 115607-115607, 2020.08, CONTEXT: Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs), catecholamine-producing tumors, represent an emerging cause of secondary osteoporosis. However, despite decreased bone mineral density (BMD), vertebral fracture (VF) is not associated with BMD in PPGLs. OBJECTIVE: To evaluate whether deteriorated bone quality is involved in the development of osteoporosis in PPGLs. PARTICIPANTS: Trabecular bone score (TBS), used to assess trabecular bone quality, was examined in 56 patients with PPGLs and 52 with non-functional adrenal tumors (AT). Radiograph of the spine was carried out in 35 patients with PPGLs, and TBS was analyzed in 18 patients with PPGLs at follow-up. MAIN OUTCOME MEASURE: TBS and BMD at the lumbar spine in patients with PPGLs with and without VF. RESULTS: PPGLs had a lower TBS (n = 56, 1.338 [1.294-1.420]) than non-functional AT (n = 52, 1.394 [1.342-1.444]; p = 0.033). Among those with PPGLs, patients with VF (n = 14, 1.314 [1.289-1.346]) had a lower TBS than those without VF (n = 21, 1.383 [1.324-1.426]; p = 0.046), despite no significant difference in BMD at the lumbar spine between the two groups (p = 0.501). An optimal cut-off level of TBS for diagnosing VF in PPGLs was 1.323, and its area under the curve was 0.702. The severity of catecholamine excess and maximal size of tumor were associated with decreased TBS in PPGLs patients (p = 0.016 and p = 0.020, respectively). Surgical resection of PPGLs improved TBS at follow-up, with 2.5% increase (p = 0.007). CONCLUSIONS: This study provides evidence for the importance of deteriorated bone quality rather than decreased bone mass in the development of VF in PPGLs..
12. Nozomi Kawata, Hirokazu Takahashi, Shinji Iwane, Kanako Inoue, Motoyasu Kojima, Michiko Kohno, Kenichi Tanaka, Hitoe Mori, Hiroshi Isoda, Satoshi Oeda, Yayoi Matsuda, Yoshiaki Egashira, Jyunichi Nojiri, Hiroyuki Irie, Yuichiro Eguchi, Keizo Anzai, FIB-4 index-based surveillance for advanced liver fibrosis in diabetes patients, Diabetology International, 10.1007/s13340-020-00453-7, 2020.07, [URL], Liver fibrosis is associated with lifestyle-related diseases, including diabetes. The identification of diabetic patients with severe liver fibrosis is important, but a simple and reliable diagnostic procedure remains to be determined. We conducted an observational study to evaluate the performance of a FIB-4 index-based screening strategy for the diagnosis of advanced liver fibrosis in patients with diabetes or prediabetes. Two hundred and forty-two patients underwent abdominal imaging in our Study. According to the abdominal imaging findings, fatty liver, liver cirrhosis, and hepatocellular carcinoma were defined, and their association with FIB-4 index evaluated. The prevalences of liver cirrhosis and hepatocellular carcinoma in patients with a high (≥ 2.67; liver cirrhosis: 42.9%, hepatocellular carcinoma: 14.3%) FIB-4 index were significantly higher than in those with an intermediate (1.3 ≤ FIB-4
13. Taisuke Narazaki, Motoaki Shiratsuchi, Takamitsu Matsushima, Mariko Tsuda, Yasuhiro Tsukamoto, Hiroki Muta, Toru Masuda, Daisaku Kimura, Akiko Takamatsu, Hidetaka Yamamoto, Yoshinao Oda, Hiroaki Miyoshi, Koichi Ohshima, Yayoi Matsuda, Ryuichi Sakamoto, Yasuhiro Nakashima, Yoshihiro Ogawa, Clinico-pathological characteristics of primary adrenal lymphomas - potential efficacy of autologous stem cell transplantation., Leukemia & lymphoma, 10.1080/10428194.2020.1725507, 61, 6, 1516-1518, 2020.06.
14. Seiichi Yano, Kenji Ashida, Ryuichi Sakamoto, Chihiro Sakaguchi, Masatoshi Ogata, Kengo Maruyama, Shohei Sakamoto, Munehiko Ikeda, Kenji Ohe, Shoko Akasu, Shimpei Iwata, Nobuhiko Wada, Yayoi Matsuda, Yoichi Nakanishi, Masatoshi Nomura, Yoshihiro Ogawa, Human leucocyte antigen DR15, a possible predictive marker for immune checkpoint inhibitor–induced secondary adrenal insufficiency, European Journal of Cancer, 10.1016/j.ejca.2020.02.049, 130, 198-203, 2020.05, [URL], Background: Immune checkpoint inhibitors (ICPis) induce various immune-related adverse events (irAEs), despite their beneficial effects in treating various advanced cancers. ICPi-induced secondary adrenal insufficiency is described as a prevalent and serious ‘pituitary irAE.’ However, its precise mechanism remains unclear, and no definitive predictive markers have been reported. Patients and methods: We enrolled and studied 11 patients with advanced cancer (aged 39–70 years; 6 male patients) receiving nivolumab, pembrolizumab or ipilimumab who developed pituitary irAEs. Their clinical data, including endocrine functions, were retrospectively assessed and human leucocyte antigen (HLA) genotypes were determined to compare the HLA allele frequencies in these patients and healthy controls. Results: Among 11 patients, 7, 3 and 1 patients exhibited malignant melanoma, non–small-cell lung cancer and gastric cancer, respectively. HLA type screening results revealed that HLA-DR15, B52 and Cw12 were observed in 9, 7, and 7 patients with pituitary irAE, respectively. DR15, B52 and Cw12 were significantly more prevalent in our group than in the healthy control group from the Japanese HLA-haplotype database (this study vs healthy control group); DR15: 81.8% vs 33.5% (n = 11, P = 0.0014), B52: 63.6% vs 21.0% (n = 11, P = 0.0026) and Cw12: 70% vs 21.3% (n = 10, P = 0.0013). Conclusions: HLA-DR15, B52 and Cw12 are possible predisposing factors for pituitary irAEs. HLA-DR15 is reportedly associated with autoimmune disease via interleukin-17 regulation, suggesting its involvement in pituitary irAE development. Using HLA haplotypes as pituitary irAE predictive markers, we could provide safe ICPi treatment and understand irAE pathogenesis..
15. Maki Yokomoto-Umakoshi, Hironobu Umakoshi, Tazuru Fukumoto, Yayoi Matsuda, Hiromi Nagata, Masatoshi Ogata, Hisaya Kawate, Takashi Miyazawa, Ryuichi Sakamoto, Yoshihiro Ogawa, Pheochromocytoma and paraganglioma
An emerging cause of secondary osteoporosis, Bone, 10.1016/j.bone.2020.115221, 133, 2020.04, [URL], Context: Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs) are catecholamine-producing neuroendocrine tumors, which are known to be associated with low bone mineral density (BMD). However, it remains unknown whether PPGLs are associated with high prevalence of osteoporotic fracture and if so, whether their surgical resection improves BMD has been addressed. Objective: To evaluate the risk of vertebral fracture (VF) in PPGLs and the improvement of BMD after surgery. Design and settings: A retrospective cross-sectional study in a single referral center. Participants: This study included the following patients: 1) 49 patients with PPGLs and 61 patients with non-functional AT who were examined radiograph of the spine, 2) 23 patients with PPGLs who were examined BMD at follow-up. Intervention: 1) The prevalence of VF was evaluated between PPGLs and non-functional AT. 2) In PPGLs, BMD was evaluated at baseline and after surgery. Results: PPGLs had a higher prevalence of VF (43% [21/49]) than non-functional AT (16% [10/61]; p = 0.002). PPGLs were associated with VF after adjusting for age and sex (odds ratio, 4.47; 95% confidence interval, 1.76–11.3; p = 0.001). In PPGLs, BMD at the lumber spine was improved (before: 0.855 ± 0.198 g/cm2, after: 0.888 ± 0.169 g/cm2, mean of the difference: 0.032 g/cm2, p = 0.026), with 3.8% increase. Conclusion: This study demonstrates that PPGLs was associated with VF and that their surgical resection contributes to the improvement of BMD in the trabecular bone. These observations support the notion that PPGLs are an emerging cause of secondary osteoporosis..
16. Hironobu Umakoshi, Ryuichi Sakamoto, Yayoi Matsuda, Maki Yokomoto-Umakoshi, Hiromi Nagata, Tazuru Fukumoto, Masatoshi Ogata, Yoshihiro Ogawa, Role of Aldosterone and Potassium Levels in Sparing Confirmatory Tests in Primary Aldosteronism, The Journal of clinical endocrinology and metabolism, 10.1210/clinem/dgz148, 105, 4, 2020.04, [URL], CONTEXT: The current clinical guidelines suggest that confirmatory tests for primary aldosteronism (PA) may be excluded in some of patients who have elevated plasma aldosterone concentration (PAC) under plasma renin suppression. However, this has low-priority evidence and is under debate in use of serum potassium. OBJECTIVE: This study aimed to investigate an appropriate setting for sparing confirmatory tests in PA. DESIGN AND SETTING: A retrospective cross-sectional study in a single referral center. PARTICIPANTS: This study included 327 patients who had hypertension under plasma renin suppression and underwent the captopril challenge test (CCT) between January 2007 and April 2019. CCT results were used to diagnose PA. MAIN OUTCOME MEASURE: Diagnostic value of PAC and serum potassium in confirmation of PA. RESULTS: Of the studied patients, 252 of 327 (77%) were diagnosed with PA. All 61 patients with PAC > 30 ng/dL were diagnosed with PA. In patients with PAC between 20 and 30 ng/dL, 44 of 55 (80%) were diagnosed with PA, while all 26 with PAC between 20 to 30 ng/dL who had spontaneous hypokalemia were diagnosed with PA. The proportion of unilateral PA determined by adrenal vein sampling (AVS) was higher in patients who had PAC > 30 ng/dL or those with spontaneous hypokalemia who had PAC between 20 and 30 ng/dL than those who did not meet the criteria (76% vs. 17%, P
17. Maki Yokomoto-Umakoshi, Ryuichi Sakamoto, Hironobu Umakoshi, Yayoi Matsuda, Hiromi Nagata, Tazuru Fukumoto, Masatoshi Ogata, Yoshihiro Ogawa, Unilateral primary aldosteronism as an independent risk factor for vertebral fracture, Clinical Endocrinology, 10.1111/cen.14145, 92, 3, 206-213, 2020.03, [URL], Context: Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. We hypothesized that the PA subtype is associated with VF. Objective: To evaluate whether unilateral PA is associated with the prevalence of VF. Design: This was a retrospective cross-sectional study in a single referral centre. Patients: We identified 210 hypertensive patients whose clinical data were available for case-detection results. One hundred and fifty-two patients were diagnosed with PA using captopril challenge tests. Measurements: We measured the prevalence of VF, according to PA subtype. Results: One hundred thirteen patients with PA were subtype classified by adrenal vein sampling. Of these, 37 patients had unilateral PA, 76 patients had bilateral PA, 58 patients had non-PA; 39 patients with PA were not subtype-classified. Patients with PA had a higher prevalence of VF (29%, 44/152) than those with non-PA (12%, 7/58; P =.011). Moreover, unilateral PA had a higher prevalence of VF (46%, 17/37) than bilateral PA (20%, 15/76; P =.021). There was no significant difference in the prevalence of VF between bilateral PA and non-PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (OR: 3.16, 95% confidence interval: 1.12-8.92; P =.017). Among patients with unilateral PA, serum cortisol concentrations after 1-mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dL) than those without (0.96 ± 0.33 g/dL; P =.048). Conclusions: Unilateral PA is an independent risk factor for VF..
18. C. Sakaguchi, K. Ashida, S. Yano, K. Ohe, N. Wada, N. Hasuzawa, Y. Matsuda, S. Sakamoto, R. Sakamoto, H. Uchi, M. Furue, M. Nomura, Y. Ogawa, A case of nivolumab-induced acute-onset type 1 diabetes mellitus in melanoma, Current oncology (Toronto, Ont.), 10.3747/co.26.4130, 26, 1, e115-e118, 2019.02, Nivolumab, an anti-PD-1 antibody, is now considered an important therapeutic agent in several advanced malignancies. However, immune-related adverse events such as endocrinopathies have been reported with its use. Thyroid disorder and isolated adrenocorticotropic hormone deficiency have frequently been reported as nivolumab-induced immune-related adverse events. Another endocrinopathy is nivolumab-induced type 1 diabetes mellitus (t1dm), described as diabetes mellitus with rapid onset and complete insulin insufficiency, at times leading to fulminant t1dm. We report the case of a 68-year-old woman who developed pancreatic islet-related autoantibody-negative t1dm, possibly induced by nivolumab, under continuous glucocorticoid administration. She was treated with nivolumab for advanced malignant melanoma, concomitant with 10 mg prednisolone daily for thrombophlebitis tapered to 5 mg after 13 courses of nivolumab therapy. At approximately the 27th course of nivolumab therapy, she showed elevated plasma glucose levels despite preserved insulin secretion. A month later, she developed diabetic ketoacidosis. Her insulin secretion decreased and finally was exhausted. She was diagnosed with acute-onset rather than fulminant t1dm because of a rapidly progressive course to diabetic ketoacidosis during just more than 1 week. She is currently receiving insulin replacement. There has been no recurrence of the melanoma. Thus, nivolumab might induce autoimmune diabetes mellitus, with patients having t1dm-sensitive human leucocyte antigen being more susceptible even when receiving glucocorticoids. Physicians should be aware that nivolumab could potentially induce t1dm as a critical immune-related adverse event..
19. Chihiro Sakaguchi, Kenji Ashida, Kenichi Kohashi, Kenji Ohe, Yoichi Fujii, Seiichi Yano, Yayoi Matsuda, Shohei Sakamoto, Ryuichi Sakamoto, Yoshinao Oda, Masatoshi Nomura, Yoshihiro Ogawa, A case of autonomous cortisol secretion in a patient with subclinical Cushing's syndrome, GNAS mutation, and paradoxical cortisol response to dexamethasone., BMC endocrine disorders, 10.1186/s12902-019-0345-8, 19, 1, 13-13, 2019.01, BACKGROUND: Increased urinary free cortisol in response to the oral administration of dexamethasone is a paradoxical reaction mainly reported in patients with primary pigmented nodular adrenocortical disease. Here, we describe the first case of subclinical Cushing's syndrome represented by autonomous cortisol secretion and paradoxical response to oral dexamethasone administration, harboring an activating mutation in the α subunit of the stimulatory G protein (GNAS). CASE PRESENTATION: A 65-year-old woman was diagnosed with subclinical Cushing's syndrome during an evaluation for bilateral adrenal masses. Tumors of unknown origin were found in the heart, brain, thyroid gland, colon, pancreas, and both adrenal glands. Adenocarcinoma of the sigmoid colon and systemic brown-patchy skin pigmentation were also present. Her urinary cortisol levels increased in response to oral dexamethasone, while serum dehydroepiandrosterone-sulfate was not suppressed. After right adrenalectomy, genetic analysis of the resected tumor revealed the somatic GNAS activating mutation, p.R201H. Paradoxical urinary cortisol response persisted even after unilateral adrenal resection, although serum and urinary cortisol levels were attenuated. CONCLUSIONS: This patient harbored a GNAS activating mutation, and presented with a mild cortisol- and androgen-producing adrenal adenoma. Administration of oral dexamethasone paradoxically increased cortisol levels, possibly via the stimulation of the cyclic adenosine monophosphate-dependent protein kinase A signaling pathway, which is seen in patients with pigmented nodular adrenocortical disease or Carney complex. GNAS mutations may provide clues to the mechanisms of hyper-function and tumorigenesis in the adrenal cortex, especially in bilateral adrenal masses accompanied by multiple systemic tumors. Examining GNAS mutations could help physicians detect extra-adrenal malignancies, which may contribute to an improved prognosis for patients with this type of Cushing's syndrome..
20. Chihiro Sakaguchi, Seiichi Yano, Kenji Ashida, Naoko Wada, Kenji Ohe, Hiromi Nagata, Yayoi Matsuda, Shohei Sakamoto, Ryuichi Sakamoto, Keizo Ohnaka, Hiroshi Uchi, Masutaka Furue, Masatoshi Nomura, Yoshihiro Ogawa, A Case of Acute Exacerbation of Chronic Adrenal Insufficiency Due to Ipilimumab Treatment for Advanced Melanoma., The American journal of case reports, 10.12659/AJCR.913021, 20, 106-110, 2019.01, BACKGROUND Ipilimumab is a therapeutic human monoclonal antibody that targets the T-cell inhibitory molecule, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and is classified as an immune checkpoint inhibitor that has been shown to improve prognosis in patients with advanced melanoma. However, several immune-related adverse events have been reported to be associated with ipilimumab Treatment. A case of acute exacerbation of chronic adrenal insufficiency is presented that highlights that glucocorticoid dosage for patients undergoing steroid treatment at the time of ipilimumab treatment has yet to be established. CASE REPORT A 50-year-old Japanese woman was diagnosed with malignant melanoma on the sole of her right foot. During her second course of ipilimumab treatment, she developed acute adrenal insufficiency caused by isolated adrenocorticotropic hormone (ACTH) deficiency, which required treatment with oral hydrocortisone. However, the symptoms of her adrenal insufficiency worsened, and she commenced treatment with 12 courses of nivolumab, a therapeutic human monoclonal antibody that blocks programmed cell death protein 1 (PD-1) on the surface of T-cells. She did not require corticosteroid support during nivolumab treatment. CONCLUSIONS This case report highlights the risk of exacerbating adrenal insufficiency during treatment with ipilimumab. The differences in clinical outcome in this patient between ipilimumab and nivolumab treatment might be explained by the different mechanisms between ipilimumab and nivolumab on immune function..
21. Hiroshi Isoda, Hirokazu Takahashi, Yuichiro Eguchi, Motoyasu Kojima, Kanako Inoue, Kenichiro Murayama, Yayoi Matsuda, Keizo Anzai, Re-evaluation of glycated hemoglobin and glycated albumin with continuous glucose monitoring system as markers of glycemia in patients with liver cirrhosis., Biomedical reports, 10.3892/br.2017.928, 7, 3, 286-286, 2017.09, [This retracts the article DOI: 10.3892/br.2016.808.]..
22. Yayoi Matsuda, Hisaya Kawate, Chitose Matsuzaki, Ryuichi Sakamoto, Kimitaka Shibue, Keizo Ohnaka, Keizo Anzai, Masatoshi Nomura, Ryoichi Takayanagi, Eplerenone improves carotid intima-media thickness (IMT) in patients with primary aldosteronism, Endocrine Journal, 10.1507/endocrj.EJ15-0362, 63, 3, 249-255, 2016.03, [URL], Primary aldosteronism (PA) is associated with a higher rate of cardiovascular events than essential hypertension. Although adrenalectomy has been reported to reduce carotid intima-media thickness (IMT) in patients with PA, the effects of the selective aldosterone blocker, eplerenone, on vascular damage in these patients remains unclear. To evaluate the effects of eplerenone on vascular status in PA patients, we sequentially measured carotid IMT (using computer software to calculate an average IMT for accurate and reproducible evaluation) in 22 patients including 8 patients treated by unilateral adrenalectomy and 14 patients treated with eplerenone for 12 months. Patients who underwent adrenalectomy showed significant reductions in aldosterone concentration (from 345 ± 176 pg/mL to 67 ± 34 pg/mL; P
23. Yasuhiro Nakashima, Motoaki Shiratsuchi, Ichiro Abe, Yayoi Matsuda, Noriyuki Miyata, Hirofumi Ohno, Motohiko Ikeda, Takamitsu Matsushima, Masatoshi Nomura, Ryoichi Takayanagi, Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy., BMC endocrine disorders, 10.1186/1472-6823-13-45, 13, 45-45, 2013.10, BACKGROUND: Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of pituitary and adrenal function after successful treatment of the lymphoma. CASE PRESENTATION: A 63-year-old Japanese man was referred to our hospital due to miosis, ptosis, hypohidrosis of his left face, polydipsia and polyuria. 18F-fluorodeoxy glucose positron emission tomography / computed tomography revealed hotspots in the pituitary gland, bilateral adrenal glands and the apex of his left lung. Surgical biopsy from the pituitary lesion confirmed the diagnosis of diffuse large B-cell lymphoma, with lymphoma cells replacing normal pituitary tissue. Endocrine function tests revealed adrenal insufficiency and panhypopituitarism, including a possible affection of the posterior pituitary. Hormone replacement therapy with desmopressin and hydrocortisone was started. Chemotherapy consisted of six courses of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) and two courses of high-dose methotrexate followed by autologous hematopoietic stem cell transplantation. Subsequently, his pituitary and bilateral adrenal lesions resolved, and serial endocrine function tests showed gradual improvement in pituitary and adrenal function. CONCLUSIONS: The present report describes an extremely rare case of diffuse large B-cell lymphoma with involvement of both the pituitary and bilateral adrenal glands. R-CHOP and high-dose methotrexate therapy followed by autologous hematopoietic stem cell transplantation was quite effective, and panhypopituitarism and adrenal insufficiency improved to almost normal values after successful treatment of the lymphoma with chemotherapy..
24. Hisaya Kawate, Michiko Kohno, Matsuda Yayoi, Yuko Akehi, Makito Tanabe, Toshihiro Horiuchi, Keizo Ohnaka, Masatoshi Nomura, Toshihiko Yanase, Ryoichi Takayanagi, Long-term study of subclinical Cushing’s syndrome shows high prevalence of extra-adrenal malignancy in patients with functioning bilateral adrenal tumors, Endocrine Journal, 10.1507/endocrj.EJ14-0155, 61, 12, 1205-1212, 2014, [URL], Subclinical Cushing’s syndrome (SCS) is characterized by subtle autonomous cortisol secretion from adrenal tumors without specific signs and symptoms of hypercortisolism. Patients with SCS have a high prevalence of “lifestylerelated diseases,” such as hypertension, diabetes mellitus, dyslipidemia, and osteoporosis. Long-term follow-up of SCS patients is reportedly indispensable for establishing indications for surgical treatment of SCS. We performed a follow-up survey of 27 patients with SCS (median: 5.3 years) and compared those who had undergone surgical treatment (n=15) with those who had not (n=12). The mean diameter of tumors was 31 mm; 16 (59%) patients had unilateral lesions and 11 (41%) carried bilateral ones. In 67% and 60% of the treatment group, respectively, hypertension and diabetes mellitus improved.We also noticed that eight of 11 (73%) SCS patients with bilateral adrenal tumors had extra-adrenal malignancies in various tissues. Interestingly, among nine SCS patients who had malignancies, eight showed bilateral adrenal uptake in 131I-aldosterol scintigraphy. The results imply that surgical treatment can reduce cardiovascular risks in SCS patients.Screening for malignancy may be necessary in patients with bilateral adrenal tumors suspected of autonomous hypersecretion of cortisol from both sides..
25. Michiko Kohno, Masatoshi Nomura, Ichiro Abe, Yusuke Matsumura, Yayoi Matsuda, Masahiro Adachi, Hisaya Kawate, Keizo Ohnaka, Takahiko Horiuchi, Ryoichi Takayanagi, A potential improvement of rheumatoid arthritis in a patient treated with liraglutide for glucocorticoid-induced diabetes, Journal of the Japan Diabetes Society, 56, 3, 179-184, 2013.03, A 74-year-old male, who had been prescribed prednisolone (PSL) for rheumatoid arthritis (RA) since age 63 and who had developed glucocorticoid-induced diabetes at age 69, was hospitalized due to poor glycemic control. On admission, he was taking 7.5 mg/day of PSL and his Hb Ale was 8.1 % despite infusion of 27 U/day of insulin. As preserved β-cell function was confirmed by a glucagon challenge test, liraglutide therapy was introduced. A stepwise increase in liraglutide successfully improved his glucose tolerance and led to discontinuation of insulin treatment A good glycemic control was finally achieved by the combination of 0.9 mg/day of liraglutide and 3 mg/day of glimepiride. Interestingly, the level of matrix metalloproteinase-3, which indicates the RA activity, was dramatically reduced from 356 ng/m/to 187 ng/m/in parallel with this treatment. The present case may imply that there is a correlation between the administration of glucagon-like peptide-1 and an improvement in the symptoms associated with rheumatoid arthritis..
26. Yayoi Matsuda, Hisaya Kawate, Shingo Shimada, Chitose Matsuzaki, Hiromi Nagata, Masahiro Adachi, Keizo Ohnaka, Masatoshi Nomura, Ryoichi Takayanagi, Perioperative sequential monitoring of hemodynamic parameters in patients with pheochromocytoma using the Non-Invasive Cardiac System (NICaS), Endocrine Journal, 10.1507/endocrj.EJ13-0471, 61, 6, 571-575, 2014, [URL], Surgical treatment of pheochromocytoma is associated with a high risk of hemodynamic instability. To reduce the risk of perioperative complications, adequate medical treatment to normalize blood pressure and restore blood volume is required. Accurate evaluation of the circulating blood volume (CBV) in perioperative patients with pheochromocytoma is clinically important. In the present study, we adopted whole-body bioimpedance monitoring technique using the Non-Invasive Cardiac System (NICaS), which can non-invasively measure cardiac output (CO) values. NICaS-derived CO values were evaluated in eight preoperative patients with pheochromocytoma and were compared with simultaneous CBV values measured by a conventional indicator dilution method using 131I-labeled human serum albumin. In these patients with pheochromocytoma, the NICaS-derived CO values were significantly correlated with the CBV values measured by 131I-labeled human serum albumin (4.86 ± 1.05 L/min vs 4.79 ± 1.02 L; r = 0.906; P = 0.002). Sequential NICaS-derived CO values confirmed that CBV increased after preoperative treatment with an α-blocker, with or without volume loading. The results of this study indicate that NICaS can be used to accurately and non-invasively evaluate the hemodynamic status. By sequential monitoring of NICaS-derived CO values, we are able to confrm whether adequate CBV in a patient with pheochromocytoma is obtained by preoperative medical treatment with α-blockers or volume loading, to avoid perioperative complications..
27. Yayoi Matsuda, Hisaya Kawate, Chitose Matsuzaki, Ryuichi Sakamoto, Ichiro Abe, Kimitaka Shibue, Michiko Kohno, Masahiro Adachi, Keizo Ohnaka, Masatoshi Nomura, Ryoichi Takayanagi, Reduced arterial stiffness in patients with acromegaly
Noninvasive assessment by the cardio-ankle vascular index (CAVI), Endocrine Journal, 10.1507/endocrj.EJ12-0189, 60, 1, 29-36, 2013, [URL], In patients with acromegaly, cardiovascular diseases are the most common cause of death. Arterial stiffness is increasingly recognized as a valuable surrogate marker for predicting cardiovascular events. To evaluate the vascular status of acromegalic patients, we used the cardio-ankle vascular index (CAVI) to reflect the arterial stiffness from the heart to the ankles. We analyzed 21 acromegalic patients, comprising five patients with untreated active acromegaly, one patient treated with medication and 15 patients who underwent transsphenoidal surgery. Among the 15 patients with surgery, 10 received additional therapies with dopamine agonists and/or somatostatin analogs. All patients with acromegaly unexpectedly showed significant reductions in the CAVI, indicating reduced arterial stiffness, compared with age- and sex-matchedcontrols, regardless of whether they underwent surgery. There was a significant negative correlation between the CAVI and the serum insulin-like growth factor (IGF)-I level in these patients. Active acromegalic patients were associated with lower CAVI than controlled patients. Sequential measurements of the CAVI and serum IGF-I before and after treatment with octreotide and transsphenoidal surgery revealed that a reduced IGF-I level after treatment was accompanied by CAVI elevation. The present findings indicate that the CAVI is negatively correlated with the serum IGF-I level in acromegaly. These findings are consistent with previous reports indicating that the GH/IGF-I axis reduces peripheral vascular resistance. This non-invasive assessment can reflect the present vascular status and would be a useful marker for evaluation of therapeutic effects in patients with acromegaly..
28. Ichiro Abe, Masatoshi Nomura, Makiko Watanabe, Shingo Shimada, Michiko Kohno, Yayoi Matsuda, Masahiro Adachi, Hisaya Kawate, Keizo Ohnaka, Ryoichi Takayanagi, Pheochromocytoma crisis caused by Campylobacter fetus, International Journal of Urology, 10.1111/j.1442-2042.2011.02950.x, 19, 5, 465-467, 2012.05, [URL], Pheochromocytoma crisis is a life-threatening endocrine emergency associated with symptoms of excess release of catecholamines. It might present spontaneously or be unmasked by triggers including trauma, surgery and certain medications that provoke catecholamine release by tumors. Here we report a case of pheochromocytoma crisis associated with abscess formation in the tumor and bacteremia of Campylobacter fetus, which was successfully treated with antibiotics and a surgical resection. This case appears to be the first reported case in the literature of abscess formation by C.fetus in pheochromocytoma, leading to catecholamine crisis..
29. Yasuhiro Nakashima, Motoaki Shiratsuchi, Ichiro Abe, Yayoi Matsuda, Noriyuki Miyata, Hirofumi Ohno, Motohiko Ikeda, Takamitsu Matsushima, Masatoshi Nomura, Ryoichi Takayanagi, Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery of their function after chemotherapy, BMC Endocrine Disorders, 10.1186/1472-6823-13-45, 13, 2013.10, [URL], Background: Diffuse large B-cell lymphoma sometimes involves the endocrine organs, but involvement of both the pituitary and adrenal glands is extremely rare. Involvement of these structures can lead to hypopituitarism and adrenal insufficiency, and subsequent recovery of their function is rarely seen. The present report describes an extremely rare case of pituitary and adrenal diffuse large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency with subsequent recovery of pituitary and adrenal function after successful treatment of the lymphoma. Case presentation: A 63-year-old Japanese man was referred to our hospital due to miosis, ptosis, hypohidrosis of his left face, polydipsia and polyuria. 18F-fluorodeoxy glucose positron emission tomography / computed tomography revealed hotspots in the pituitary gland, bilateral adrenal glands and the apex of his left lung. Surgical biopsy from the pituitary lesion confirmed the diagnosis of diffuse large B-cell lymphoma, with lymphoma cells replacing normal pituitary tissue. Endocrine function tests revealed adrenal insufficiency and panhypopituitarism, including a possible affection of the posterior pituitary. Hormone replacement therapy with desmopressin and hydrocortisone was started. Chemotherapy consisted of six courses of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) and two courses of high-dose methotrexate followed by autologous hematopoietic stem cell transplantation. Subsequently, his pituitary and bilateral adrenal lesions resolved, and serial endocrine function tests showed gradual improvement in pituitary and adrenal function. Conclusions: The present report describes an extremely rare case of diffuse large B-cell lymphoma with involvement of both the pituitary and bilateral adrenal glands. R-CHOP and high-dose methotrexate therapy followed by autologous hematopoietic stem cell transplantation was quite effective, and panhypopituitarism and adrenal insufficiency improved to almost normal values after successful treatment of the lymphoma with chemotherapy..
30. Yayoi Matsuda, Hisaya Kawate, Yuka Okishige, Ichiro Abe, Masahiro Adachi, Keizo Ohnaka, Naoichi Satoh, Junichi Inokuchi, Katsunori Tatsugami, Seiji Naito, Masatoshi Nomura, Ryoichi Takayanagi, Successful management of cryptococcosis of the bilateral adrenal glands and liver by unilateral adrenalectomy with antifungal agents
A case report, BMC Infectious Diseases, 10.1186/1471-2334-11-340, 11, 2011.12, [URL], Background: Cryptococcus species usually affect the central nervous system and lungs in immunocompromised hosts. Although the adrenal glands can be involved in disseminated cryptococcosis, primary adrenal insufficiency caused by the fungal infection is uncommon.Case presentation: We present a case of primary adrenal insufficiency with bilateral adrenal masses and liver invasion in a 43-year-old man with mild type 2 diabetes mellitus. Cryptococcosis was diagnosed by fine-needle aspiration biopsy of the liver mass. The serum cryptococcal antigen titer was elevated to 1:256. After 6 months of antifungal therapy with fluconazole and amphotericin B, the size of the liver mass was decreased, but no significant changes were observed in the bilateral adrenal masses and the serum cryptococcal antigen titer remained elevated at 1:128. To control the cryptococcosis, a laparoscopic left adrenalectomy was performed, followed by antifungal therapy. After the unilateral adrenalectomy, the size of the remaining right adrenal mass was reduced and the serum cryptococcal antigen titer declined to 1:4.Conclusions: This is the first report describing adrenal cryptococcosis with adrenal insufficiency and liver invasion without central nervous system involvement. Adrenal cryptococcosis should be considered in the differential diagnosis for patients with bilateral adrenal masses with primary adrenal deficiency. Unilateral adrenalectomy was quite effective in controlling the cryptococcosis in this case. Even in patients with bilateral adrenal cryptococcosis, unilateral adrenalectomy should be an option for treatment of disseminated cryptococcosis..
31. Yuka Fujii, Yoshito Mizoguchi, Jun Masuoka, Yayoi Matsuda, Tatsuya Abe, Keizo Anzai, Yutaka Kunitake, Hiroshi Tateishi, Takayoshi Inaba, Toru Murakawa, Takahiro A. Kato, Akira Monji, Cushing’s syndrome and psychosis
A case report and literature review, Primary Care Companion to the Journal of Clinical Psychiatry, 10.4088/PCC.18br02279, 20, 5, 2018, [URL], Psychiatric complications of Cushing’s syndrome include irritability, anxiety, depressed mood, and cognitive impairment. Psychosis is a rare manifestation of Cushing’s syndrome; therefore, the literature on the subject is limited and consists mainly of clinical case reports. We report a case of Cushing’s syndrome misdiagnosed as schizophrenia-like psychosis for more than 10 years. Transsphenoidal adenomectomy resulted in amelioration of psychiatric symptoms as well as improvement of cognitive ability. Clinicians should consider the presence of psychiatric symptoms predating the diagnosis of Cushing’s syndrome, especially when these symptoms are persistent and treatment-resistant, as seen in the present case..

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