Ishii, Tomohiro

写真a

Affiliation

School of Medicine, Department of Pediatrics （Shinanomachi）

Position

Associate Professor

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Career 【 Display / hide 】

  • 1992.04
    -
    1994.06

    Keio University School of Medicine,, Department of Pediatrics, Resident (Pediatrics)

  • 1996.07
    -
    1998.07

    Ota General Hospital, Department of Pediatrics, Residenct (Pediatrics)

  • 1998.08
    -
    2000.06

    Keio University School of Medicine, Department of Pediatrics, Instructor

  • 2000.07
    -
    2005.03

    University of Texas Southwestern Medical Center, Division of Endocrinology and Metabolism, Department of internal medicine, Postdoctoral research fellow

  • 2005.04
    -
    2013.04

    Keio University School of Medicine, Department of Pediatrics, Instructor

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Academic Background 【 Display / hide 】

  • 1986.04
    -
    1992.03

    Keio University, School of Medicine

    University, Graduated

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Academic Degrees 【 Display / hide 】

  • Steroidogenic acute regulatory protein欠損マウスの表現型における高密度リポ蛋白と性腺刺激ホルモンの関与, Keio University, Dissertation

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Licenses and Qualifications 【 Display / hide 】

  • Medical licence

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Research Areas 【 Display / hide 】

  • Life Science / Metabolism and endocrinology

  • Life Science / Embryonic medicine and pediatrics

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Research Keywords 【 Display / hide 】

  • steroid hormone

  • Adrenal cortex

  • Adrenal insufficiency

  • Disorders of sex development

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Research Themes 【 Display / hide 】

  • Mechanism of cholesterol transfer by steroidogenic acute regulatory protein, 

    2000.06
    -
    Present

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Books 【 Display / hide 】

  • Cellular endocrinology in health and disease

    ISHII TOMOHIRO, Academic Press, 2014.03

    Scope: Transcriptome analysis of adrenocortical cells in health and disease

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Papers 【 Display / hide 】

  • Combination therapy of propranolol, levothyroxine, and liothyronine was effective in a case of severe consumptive hypothyroidism associated with infantile hepatic hemangioma

    Osada A., Araki E., Yamashita Y., Ishii T.

    Clinical Pediatric Endocrinology （Clinical Pediatric Endocrinology)  28 （ 1 ） 9 - 14 2019

    ISSN  09185739

    　View Summary

    © 2019 by The Japanese Society for Pediatric Endocrinology. Infantile hepatic hemangioma (IHH) can be accompanied by consumptive hypothyroidism. We report the case of a 4-mo-old boy who showed massive hepatomegaly, peripheral coldness, lethargy, and failure to thrive. An enhanced computed tomography scans demonstrated multiple hemangiomas in both lobes of the liver, and a thyroid function tests showed severe hypothyroidism: TSH 561.5 µIU/mL, free triiodothyronine (fT 3 ) 1.0 pg/mL, and free thyroxine (fT 4 ) < 0.7 ng/dL. IHH gradually regressed following propranolol treatment and fT 4 increased to a low normal level (1.0 ng/dL) by high dose replacement of levothyroxine, while fT 3 remained very low (< 1.0 pg/mL), even following high doses of levothyroxine; fT 3 eventually normalized following the administration of liothyronine. We suggest that treatment strategies should be individualized based on thyroid function, and that the combination therapy of propranolol for anti-tumor treatment and levothyroxine and liothyronine for respective thyroid hormone replacement is effective, particularly in cases of severe consumptive hypothyroidism due to multiple IHHs.

  • In vivo verification of the pathophysiology of lipoid congenital adrenal hyperplasia in the adrenal cortex

    Mizuno Y., Ishii T., Hasegawa T.

    Endocrinology （Endocrinology)  160 （ 2 ） 331 - 338 2019

    ISSN  00137227

    　View Summary

    Copyright © 2019 Endocrine Society A two-hit hypothesis has been proposed to describe the pathophysiology of lipoid congenital adrenal hyperplasia. In previous studies using conventional steroidogenic acute regulatory protein (Star) gene knockout (KO) mice, adrenocortical lipid accumulation was already prominent at birth. Thus, the two-hit hypothesis was verified in the gonads of Star KO mice but not in the adrenal cortices. We generated time-dependent conditional Star KO mice induced by tamoxifen (TAM) injections and analyzed the adrenal cortices of the mice histologically and endocrinologically before, 24 hours after, and 8 weeks after TAM. We performed RNA sequencing analyses of the adrenal glands before and 8 weeks after TAM and histologically analyzed autologous adrenal cortices of TAM-induced Star KO mice with transplantation of wild-type adrenal gland. Lipid accumulation was scattered 24 hours after TAM and was prominent 8 weeks after TAM. Steroidogenic capacity decreased sequentially after TAM. Gene expression related to steroid biosynthesis significantly decreased 8 weeks after TAM compared with that before TAM. TAM-induced Star KO mice with adrenal transplantation showed normal ACTH levels and mild lipid accumulation. These results showed that the steroidogenic capacity decreased without histological change (the first hit) and declined with histological change (the second hit). Thus, we visualized the two-hit hypothesis in the adrenal cortex. The key feature of the secondary decline of steroidogenic capacity might be the decreased gene expression related to steroid biosynthesis after lipid accumulation exacerbated by ACTH hypersecretion.

  • MIRAGE syndrome is a rare cause of 46,XY DSD born SGA without adrenal insufficiency

    Shima H., Hayashi M., Tachibana T., Oshiro M., Amano N., Ishii T., Haruna H., Igarashi M., Kon M., Fukuzawa R., Tanaka Y., Fukami M., Hasegawa T., Narumi S.

    PLoS ONE （PLoS ONE)  13 （ 11 ）  2018.11

    　View Summary

    © 2018 Shima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background MIRAGE syndrome, a congenital multisystem disorder due to pathogenic SAMD9 variants, describes a constellation of clinical features including 46,XY disorders of sex development (DSD), small for gestational age (SGA) and adrenal insufficiency (AI). It is poorly understood whether SAMD9 variants underlie 46,XY DSD patients born SGA (46,XY DSD SGA) without AI. This study aimed to define the frequency and phenotype of SAMD9 variants in 46,XY DSD SGA without AI. Methods Forty-nine Japanese patients with 46,XY DSD SGA (Quigley scale, 2 to 6; gestational agematched birth weight percentile, <10) without history of AI were enrolled. The single coding exon of SAMD9 was PCR-amplified and sequenced for each patient. Pathogenicity of an identified variant was verified in vitro. Placenta tissues were obtained from the variant-carrying patient, as well as from another previously described patient, and were analyzed histologically. Results In one 46,XY DSD SGA patient, a novel heterozygous SAMD9 variant, p.Phe1017Val, was identified. Pathogenicity of the mutant was experimentally confirmed. In addition to DSD and SGA, the patient had neonatal thrombocytopenia, severe postnatal grow restriction, chronic diarrhea and susceptibility to infection, all features consistent with MIRAGE, leading to premature death at age 14 months. The patient did not have any manifestations or laboratory findings suggesting AI. Placenta tissues of the two variant-carrying patients were characterized by maldevelopment of distal villi without other findings of maternal underperfusion. Conclusions MIRAGE syndrome is a rare cause of 46,XY DSD SGA without AI. This study exemplifies that AI is a common feature of MIRAGE syndrome but that the absence of AI should not rule out a diagnosis of the syndrome.

  • Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years with 21-Hydroxylase Deficiency: A Nationwide Survey in Japan

    Ishii T., Adachi M., Takasawa K., Okada S., Kamasaki H., Kubota T., Kobayashi H., Sawada H., Nagasaki K., Numakura C., Harada S., Minamitani K., Sugihara S., Tajima T.

    Hormone Research in Paediatrics （Hormone Research in Paediatrics)  89 （ 3 ） 166 - 171 2018.04

    ISSN  16632818

    　View Summary

    © 2018 S. Karger AG, Basel. Copyright: All rights reserved. Background/Aims: We aimed to evaluate the incidence and characteristics of adrenal crisis in Japanese children with 21-hydroxylase deficiency (21-OHD). Methods: We conducted a retrospective nationwide survey for the councilors of the Japanese Society for Pediatric Endocrinology (JSPE) regarding adrenal crisis in children under 7 years with 21-OHD, admitted to hospitals from 2011 through 2016. We defined adrenal crisis as the acute impairment of general health due to glucocorticoid deficiency with at least two of symptoms, signs, or biochemical abnormalities. Results: The councilors of the JSPE in 83 institutions responded to this survey (response rate, 60.1%). Data analyses of 378 patients with 1,101.4 person-years (PYs) revealed that 67 patients (17.7%) experienced at least 1 episode of hospital admission for adrenal crisis at the median age of 2 years. The incidence of adrenal crisis was calculated as 10.9 per 100 PYs (95% confidence interval [CI] 9.6-12.2). Infections were the most common precipitating factors, while no factor was observed in 12.5%. Hypoglycemia occurred concomitantly in 27.4%. One patient died from severe hypoglycemia, resulting in a mortality rate of 0.09 per 100 PYs (95% CI 0.0-0.2). Conclusion: Adrenal crisis is not rare and can be accompanied by disastrous hypoglycemia in children with 21-OHD.

  • Incidence and Characteristics of Adrenal Crisis in Children Younger than 7 Years with 21-Hydroxylase Deficiency

    Ishii Tomohiro, Adachi Masanori, Takasawa Kei, Okada Satoshi, Kamasaki Hotaka, Kubota Takuo, Kobayashi Hironori, Sawada Hirotake, Nagasaki Keisuke, Numakura Chikahiko, Harada Shohei, Minamitani Kanshi, Sugihara Shigetaka, Tajima Toshihiro

    Hormone Research in Paediatrics  2018.02

    ISSN  1663-2818

    　View Summary

    <p>Background/Aims: We aimed to evaluate the incidence and characteristics of adrenal crisis in Japanese children with 21-hydroxylase deficiency (21-OHD). Methods: We conducted a retrospective nationwide survey for the councilors of the Japanese Society for Pediatric Endocrinology (JSPE) regarding adrenal crisis in children under 7 years with 21-OHD, admitted to hospitals from 2011 through 2016. We defined adrenal crisis as the acute impairment of general health due to glucocorticoid deficiency with at least two of symptoms, signs, or biochemical abnormalities. Results: The councilors of the JSPE in 83 institutions responded to this survey (response rate, 60.1%). Data analyses of 378 patients with 1,101.4 person-years (PYs) revealed that 67 patients (17.7%) experienced at least 1 episode of hospital admission for adrenal crisis at the median age of 2 years. The incidence of adrenal crisis was calculated as 10.9 per 100 PYs (95% confidence interval [CI] 9.6–12.2). Infections were the most common precipitating factors, while no factor was observed in 12.5%. Hypoglycemia occurred concomitantly in 27.4%. One patient died from severe hypoglycemia, resulting in a mortality rate of 0.09 per 100 PYs (95% CI 0.0–0.2). Conclusion: Adrenal crisis is not rare and can be accompanied by disastrous hypoglycemia in children with 21-OHD.</p>

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

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Reviews, Commentaries, etc. 【 Display / hide 】

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

  • Identification of adrenogonadal progenitor cells in the gonads which can be reprogrammed into adrenal steroidogenic cells

    2019.04
    -
    2022.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • リポイド副腎過形成症モデルマウスと細胞株によるステロイドホルモン生合成機構の 解明

    2016.04
    -
    2019.03

    Grant-in-Aid for Scientific Research, Research grant, Principal investigator

  • 次世代遺伝子解析装置を用いた46,XY性分化疾患の責任遺伝子-表現型の関連解析と新規責任遺伝子の同定

    2014.04
    -
    2015.03

    公益財団法人 川野小児医学奨学財団, 川野正登記念研究助成, Research grant, Principal investigator

  • 内因性ステロイドホルモン産生制御機構下におけるsteroidogenic acute regulatory proteinの機能解析と先天性リポイド副腎過形成症の副腎・性腺リモデリングの病態解析

    2014.04
    -
    2015.03

    公益財団法人小児医学研究振興財団, 研究助成金, Research grant, Principal investigator

  • StAR欠損マウスのステロイドホルモン産生細胞におけるトランスクリプトーム解析

    2011.04
    -
    2014.03

    Grant-in-Aid for Scientific Research, Research grant, Principal investigator

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Awards 【 Display / hide 】

  • Young Investigator’s Award in 2nd Congress of Asian Society for Pediatric Research

    2006.12

  • Travel Award in The Endocrine Society’s 88th annual meeting

    2006.06

  • 日本小児科学会　学術研究賞

    2016.05, Japan Pediatric Society

  • Science Award

    2014.09, Japanese Society for Pediatric Endocrinology

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Courses Taught 【 Display / hide 】

  • LECTURE SERIES, PEDIATRICS

    2022

  • INTRODUCTION TO MEDICINE

    2022

  • LECTURE SERIES, PEDIATRICS

    2021

  • LECTURE SERIES, PEDIATRICS

    2020

  • LECTURE SERIES, PEDIATRICS

    2019

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Courses Previously Taught 【 Display / hide 】

  • Growth, development, and maturation

    Keio University

    2018.04
    -
    2019.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

  • Neonatal mass screening

    Keio University

    2018.04
    -
    2019.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

  • Neonatal mass screening

    Keio University

    2017.04
    -
    2018.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

  • Neonatal mass screening

    Keio University

    2016.04
    -
    2017.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

  • Neonatal mass screening

    Keio University

    2015.04
    -
    2016.03
    , 

    Spring Semester, Lecture, Within own ｆaculty

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Memberships in Academic Societies 【 Display / hide 】

  • The Japan Pediatric Society

    　

  • The Japanese Society for Pediatric Endocrinology

    　

  • The Japan Endocrine Society

    　

  • The Endocrine Society

    　

  • The Japan Society of Human Genetics

    　
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Committee Experiences 【 Display / hide 】

  • 2017.09
    -
    Present

    理事, 日本小児内分泌学会

  • 2017.05
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    Present

    評議員, 日本生殖内分泌学会

  • 2015.07
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    Present

    評議員, 日本人類遺伝学会

  • 2014.07
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    Present

    成長ホルモン治療研究専門委員, 成長科学協会

  • 2013.07
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    Present

    東京都地区委員, 成長科学協会

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