Kurihara, Isao



School of Medicine, Department of Internal Medicine (Nephrology, Endocrinology and Metabolism) (Shinanomachi)


Assistant Professor/Senior Assistant Professor

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Papers 【 Display / hide

  • Impact of adrenocorticotropic hormone stimulation during adrenal venous sampling on outcomes of primary aldosteronism

    Takeda Y., Umakoshi H., Takeda Y., Yoneda T., Kurihara I., Katabami T., Ichijo T., Wada N., Yoshimoto T., Ogawa Y., Kawashima J., Sone M., Takahashi K., Watanabe M., Matsuda Y., Kobayashi H., Shibata H., Kamemura K., Otsuki M., Fujii Y., Yamamto K., Ogo A., Yanase T., Suzuki T., Naruse M.

    Journal of hypertension (Journal of hypertension)  37 ( 5 ) 1077 - 1082 2019.05

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    BACKGROUND: Adrenal venous sampling (AVS) is essential for identifying a surgically curable form of primary aldosteronism. Adrenocorticotropic hormone (ACTH) infusion or bolus has been reported to improve the success rate of AVS, although the effects on lateralization and its outcomes in unilateral primary aldosteronism are unclear. METHODS: The success rate and lateralization indices were examined in a cohort of 2197 Japanese patients with primary aldosteronism from 28 centres who underwent AVS. Outcomes were analysed in 267 patients with aldosterone-producing adenomas (APAs). RESULTS: ACTH loading during AVS improved the success rate from 67 to 89%, while lateralization indices decreased from 62 to 28%. Bolus, bolus along with continuous infusion or continuous infusion of ACTH did not affect both indices. The absence of clinical success (i.e. unchanged or increased blood pressure) was 33% and absence of biochemical success (persistent hypokalaemia or persistently raised aldosterone-to-renin ratio, or both) was 15%. The clinical and biochemical success rates did not differ between the three groups [lateralization index >2 in basal condition (LIb) and lateralization index >4 after ACTH loading (lateralization indices), and LIb >2 + lateralization indices<4, LIb<2+lateralization indices>4]. The three groups (LIb>4+lateralization indices>4, LIb>4+lateralization indices<4 and LIb<4+lateralization indices>4) did not show any significant differences of clinical and biochemical outcome. CONCLUSION: ACTH loading during AVS improved the success rate but decreased laterality. ACTH did not affect the clinical and biochemical outcomes in APA patients. These data showed that the use of ACTH during AVS was helpful for improving the success rate, but did not contribute to better outcomes.

  • Usefulness of hemoglobin a1c and glycated albumin measurements for insulinoma screening: An observational case-control study

    Torimoto K., Okada Y., Tanaka Y., Matsuoka A., Hirota Y., Ogawa W., Saisho Y., Kurihara I., Itoh H., Inada S., Koga M.

    BMC Cancer (BMC Cancer)  19 ( 1 )  2019.02

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    © 2019 The Author(s). Background: Insulinoma represents hypoglycemia as a predominant symptom; the autonomic symptoms may be resolved by chronically recurrent hypoglycemia resulting in the persistence of non-specific symptoms alone. Therefore, it has been estimated that there are many patients in whom the disease takes longer to diagnose and has remained undiagnosed. Although some parameters exist for the definitive diagnosis of the disease, there are currently no indices for early screening. Indices of glycemic control, hemoglobin A1c (HbA1c), and glycated albumin (GA) may be useful for the screening of patients with insulinoma having chronic hypoglycemia because the values become low in such a condition. Because there are no articles that have reported the point, we examine the effective cutoff values of HbA1c and GA for the diagnosis of insulinoma in the present study. Methods: In a multicenter cross-sectional study, 31 patients with insulinoma were included for comparison with 120 control subjects with normal glucose tolerance based on 75 g oral glucose tolerance tests whose characteristics were matched to the patients. The primary outcomes were optimal cutoff values of HbA1c and GA for the screening of insulinoma. Results: HbA1c was significantly lower in the insulinoma group at 4.7 ± 0.4% compared to the healthy control group at 5.7 ± 0.3% (p < 0.001), and GA was significantly lower in the insulinoma group at 11.6 ± 1.8% compared to the healthy control group at 14.5 ± 1.0% (p < 0.001). According to a receiver operating characteristic (ROC) analysis, optimal cutoff values of HbA1c and GA for the diagnosis of insulinoma were 5.0 and 12.4%, respectively. Area under the curve values of HbA1c and GA were 0.970 and 0.929, respectively, showing no significant difference (p = 0.399). Conclusions: In the present study, HbA1c and GA values in patients with insulinoma were significantly lower compared to the healthy controls, and effective cutoff values for screening were shown in the diagnosis of insulinoma for the first time. HbA1c and GA can be useful indices for insulinoma screening. Because malignant insulinoma have a similar diagnostic process to that of benign insulinoma, these could be useful for malignant insulinoma.

  • Organ memory: a key principle for understanding the pathophysiology of hypertension and other non-communicable diseases

    Itoh H., Kurihara I., Miyashita K.

    Hypertension Research (Hypertension Research)  41 ( 10 ) 771 - 779 2018.10

    ISSN  09169636

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    © 2018, The Japanese Society of Hypertension. In recent years, several post-interventional analyses of large-scale randomized controlled clinical trials have given us a new concept regarding the risk management of hypertension and cardiovascular diseases. The beneficial effects of intensive treatments were extended even after the interventions ended. This phenomenon is known as “metabolic memory” or “legacy effect”, and we recognized its clinical significance. A certain level of evidence in human and animal studies employing organ transplantation techniques has indicated that this type of “memory” resides in each organ and could be transferrable, erasable, and rewritable, which is similar to neuronal and immune “memory”. In this review, we define this memory as “organ memory” and summarize the current picture and future direction of this concept. “Organ memory” can be observed in many clinical settings, including in the control of hypertension, diabetes mellitus, and dyslipidemia. Several intensive treatments were demonstrated to have the potential to rewrite “organ memory”, leading to the curability of targeted diseases. “Organ memory” is the engraved phenotype of altered organ responsiveness acquired by a time-dependent accumulation of organ stress responses. Not only is the epigenetic change of key genes involved in the formation of “organ memory” but the alteration of multiple factors, including low molecular weight energy metabolites, immune mediators, and tissue structures, is involved as well. These factors intercommunicate during every stress response and carry out incessant remodeling in a certain direction in a spiral fashion through positive feedback mechanisms. Future studies should be directed toward the identification of the core unit of “organ memory” and its manipulation.

  • Clinical characteristics and postoperative outcomes of primary aldosteronism in the elderly

    Takeda M., Yamamoto K., Akasaka H., Rakugi H., Naruse M., Takeda Y., Kurihara I., Itoh H., Umakoshi H., Tsuiki M., Ichijo T., Katabami T., Wada N., Shibayama Y., Yoshimoto T., Ogawa Y., Kawashima J., Sone M., Inagaki N., Takahashi K., Fujita M., Watanabe M., Matsuda Y., Kobayashi H., Shibata H., Kamemura K., Otsuki M., Fujii Y., Ogo A., Okamura S., Miyauchi S., Yanase T., Suzuki T., Kawamura T.

    Journal of Clinical Endocrinology and Metabolism (Journal of Clinical Endocrinology and Metabolism)  103 ( 10 ) 3620 - 3629 2018.10

    ISSN  0021972X

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    © 2018 Oxford University Press. All rights reserved. Context: Primary aldosteronism (PA) in the elderly has increased in importance in association with population aging. Objective: To investigate the characteristics and outcomes of elderly patients with PA undergoing adrenalectomy. Patients and Methods: Using a database of patients with PA who underwent adrenal venous sampling (AVS),wecompared elderly patients (65 years old)with nonelderly patients (,65 years old) in terms of characteristics, subtype classification in ACTH-stimulated AVS, and outcomes after adrenalectomy. Results: The elderly group had a higher prevalence of comorbidities than the nonelderly group. The proportion of the unilateral subtype [defined as a lateralization index (LI) .4] was comparable between the age groups. In patients who received adrenalectomy, biochemical cure was comparable between the groups, whereas persistent hypertension was more common in the elderly group. The prevalences of hyperkalemia and renal impairment (chronic kidney disease stage 3b or higher) were higher in the elderly group. Multiple regression analysis showed that the duration of hypertension predicted persistent hypertension and hyperkalemia and that preoperative estimated glomerular filtration rate predicted renal impairment in the elderly group. LI .4 in AVS was an independent predictor of biochemical cure after adrenalectomy in the elderly group but not in the nonelderly group. Age was negatively associated with biochemical cure in patients with LI #4. Conclusion: Adrenalectomy contributes to biochemical improvement in elderly patients if determined in accordance with AVS. The treatment strategy should be determined considering the high postoperative incidence of persistent hypertension and hyperkalemia in elderly patients with a long history of hypertension or renal impairment in those with reduced renal function.

  • Epidermal growth factor receptor/extracellular signal-regulated kinase pathway enhances mineralocorticoid receptor transcriptional activity through protein stabilization

    Mitsuishi Y., Shibata H., Kurihara I., Kobayashi S., Yokota K., Murai-Takeda A., Hayashi T., Jo R., Nakamura T., Morisaki M., Itoh H.

    Molecular and Cellular Endocrinology (Molecular and Cellular Endocrinology)  473   89 - 99 2018.09

    ISSN  03037207

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    © 2018 Elsevier B.V. Activation of mineralocorticoid receptor (MR) is evoked by aldosterone, and it induces hypertension and cardiovascular disease when it's concomitant with excessive salt loading. We have proposed the notion of “MR-associated hypertension” in which add-on therapy of MR blockers is effective even though serum aldosterone level is within normal range. To elucidate its underlying molecular mechanism, we focused on the effect of epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) activation on MR activity. Epidermal growth factor (EGF) administration increased MR transcriptional activity through EGFR/ERK pathway and increased protein level by counteracting MR ubiquitylation in vitro. EGF administration in vivo also increased MR protein level and target gene expression in kidney, which were decreased by EGFR inhibitor. In addition, the administration of EGFR inhibitor lowered systolic blood pressure and MR activity in DOCA/salt-treated mice. In conclusion, EGFR/ERK pathway activation is considered as one of the underlying mechanisms of aberrant MR activation and EGFR/ERK pathway blockade could be an alternative approach for the prevention of MR-related cardiovascular events.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • Association between severity of obstructive sleep apnea and glycated hemoglobin level in japanese individuals with and without diabetes

    Kurosawa H., Saisho Y., Fukunaga K., Haraguchi M., Yamasawa W., Kurihara I., Betsuyaku T., Itoh H.

    Endocrine Journal (Endocrine Journal)  65 ( 1 ) 121 - 127 2018

    ISSN  09188959

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    © The Japan Endocrine Society. Aim of this study was to examine the association between the severity of obstructive sleep apnea (OSA) and dysglycemia in Japanese individuals with and without type 2 diabetes (T2DM). We enrolled 115 individuals diagnosed with OSA with an apnea hypopnea-index (AHI) ≥ 20 in whom continuous positive airway pressure (CPAP) therapy was introduced (N = 115, 44 with T2DM, age 62 ± 11 years, BMI 27.0 ± 4.4 kg/m2 and AHI median 36.1; interquartile range 27.2–48.1). During admission, the severity of OSA was evaluated by polysomnography, and its association with glycated hemoglobin (HbA1c) level was examined. Continuous glucose monitoring (CGM) was also conducted during the admission in 94 individuals. Apnea-hypopnea index (AHI), non-rapid eye movement (REM) AHI, minimum peripheral capillary oxygen saturation (SpO2) and percentage of sleep time (%TST) with SpO2 < 90% were significantly associated with HbA1c level in total and non-diabetic individuals (all p < 0.05) but not in those with T2DM, the majority of whom were treated with anti-diabetic medications. The associations of the non-REM AHI and %TST with SpO2 < 90% with HbA1c level remained significant after adjustment for age, sex and BMI in non-diabetic and T2DM subjects treated with dietary therapy only. Mean glucose level, but not SD or coefficient of variation of glucose, assessed by CGM was significantly associated with AHI and non-REM AHI in non-diabetic subjects after adjustment for age, sex and BMI. In conclusion, the severity of OSA was associated with increased HbA1c level independently of BMI in Japanese individuals, especially in those without diabetes.

Presentations 【 Display / hide

  • 原発性アルドステロン症の確定診断における経口食塩負荷試験および立位フロセミドレニン刺激試験の有用性の検討

    村井 彩乃、柴田 洋孝、小林 佐紀子、須田 徳子、横田 健一、栗原 勲、本間 桂子、太田 敦美。林 晃一、齊藤 郁夫、猿田 享男

    第78回日本内分泌学会 (東京) , 2005.07, Oral Presentation(general)

  • 副腎腫瘍症例におけるACTH負荷血中17-hydroxyprogesterone(17OHP)および尿中pregnanetriolonr(Ptl)の検討

    小林 佐紀子、柴田 洋孝、本間 桂子、須田 徳子、横田 健一、村井 彩乃、栗原 勲、林 晃一、齊藤 郁夫、猿田 享男

    第78回日本内分泌学会 (東京) , 2005.07, Oral Presentation(general)

  • COUP-TFI and transcriptional coregulators in adrenal cortical steroidogenesis

    Shibata Hirotaka, Kurihara Isao, Kobayashi Sakiko, Ikeda Yayoi, Yokota Kenichi, Saito Ikuo, Rainey William, White Perrin, Saruta Takao

    The 2nd International Nuclear Receptor Meeting, 2003.03, Oral Presentation(guest/special)

  • 経口糖負荷試験で糖尿病型でなく腎生検で糖尿病性腎症と診断された一例

    Jou Yuusuke, Eguchi Takashi, Kurihara Isao, Ichihara Atsuhiro, Hashiguchi Akinori, Konishi Kounosuke, Hayashi Matsuhiko, Saruta Takao

    第32回日本腎臓学会東部学術大会, 2002.10, Poster (general)

  • 核内受容体COUP-TFに結合する新規転写共役因子CIP-1のクローニング

    Kobayashi Sakiko, Shibata Hirotaka, Kurihara Isao, Hayashi Matsuhiko, Saitou Ikuo, Saruta Takao

    第75回日本内分泌学会学術総会, 2002.06, Oral Presentation(general)

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 糖尿病性腎症の病態形成における腸管ミネラルコルチコイド受容体機能の関与の検討


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 栗原 勲, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 組織特異的遺伝子改変マウスを用いた心血管リスク管理における腸管MRの意義の解明


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 栗原 勲, Grant-in-Aid for Scientific Research (C), Principal Investigator


Courses Taught 【 Display / hide











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