Details of a Researcher - Narumi, Satoshi

Papers - Narumi, Satoshi

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Within-individual changes in BMI and menstrual irregularity: a cohort study using real-world data

Itoi S., Sampei M., Tatsumi T., Ishida R., Izumi G., Osuga Y., Koga K., Narumi S., Morisaki N.

BMC Women S Health 26 ( 1 ) 2026.12

Background: The impact of body mass index (BMI) on reproductive health is well-established, but the effect of within-individual changes in BMI on the menstrual cycle, a valuable and accessible indicator of reproductive health, remains less studied. This study aimed to investigate the association between changes in individuals’ BMI and menstrual irregularity. Methods: This cohort study analyzed data from a widely used menstrual tracking app in Japan. Menstrual cycle logs were collected from January 2019 to March 2021, and background information from questionnaires (Wave 1: Jan-Mar 2020; Wave 2: May-Jun 2020). Long-term BMI changes were defined as changes from age 18 to Wave 2, and short-term changes were defined as changes from Wave 1 to Wave 2. BMI was categorized as underweight (15–18.4), normal (18.5–22.9), and overweight/obese (23–35). Menstrual irregularity was defined as an individual’s average cycle length ranging outside the 24–38 day range. Results: A total of 126,008 cycles from 5,444 individuals were analyzed. Individuals with overweight/obesity who became normal weight long-term had significantly lower odds of menstrual irregularity (long-term: aOR 0.39, 95% CI 0.20–0.75; short-term: aOR 0.61, 95% CI 0.18–2.02) compared to those who remained overweight/obese. Conversely, increases from normal weight to overweight/obese increased the odds (long-term: aOR 2.02, 95% CI 1.50–2.71; short-term: aOR 2.53, 95% CI 1.31–4.90) compared to those who remained normal weight. No significant association was found for individuals with underweight. Conclusion: Within-individual changes in BMI influence menstrual irregularity. Long-term, but not short-term, reductions from overweight/obese BMI to the normal BMI category were associated with lower odds of irregular cycles, whereas increases from a normal BMI to overweight/obesity raised the risk. These findings highlight the importance of sustainable weight management in enhancing reproductive health.

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A 1-year-old boy with MIRAGE syndrome and nephrotic syndrome, whose kidney histopathology revealed membranous nephropathy-like findings: a case report

Ishimori S., Imaide A., Yokota T., Narumi S., Yoshikawa N.

Pediatric Nephrology 41 ( 2 ) 357 - 360 2026.02

ISSN 0931041X

MIRAGE syndrome is a rare multisystem disorder caused by gain-on-function SAMD9 variants. Kidney biopsies in some MIRAGE syndrome patients have shown glomerular sclerosis or interstitial nephritis. A boy with genetically confirmed MIRAGE syndrome, who showed microhematuria and nephrotic range proteinuria, underwent kidney biopsy at 18 months, revealing diffuse mesangial proliferation and partial segmental lobular accentuation associated with mesangial cell proliferation with neither crescentic lesions nor sclerotic glomeruli. Immunofluorescence staining showed diffuse granular deposition of IgG along the glomerular basement membrane and dominant deposition of IgG in the mesangial matrix. Electron microscopy revealed diffuse subepithelial electron-dense deposits. Treatment with prednisolone for membranous nephropathy-like findings was initiated but the proteinuria persisted. At 21 months of age, the patient died of multi-organ failure as a result of severe gastrointestinal infection and necrotizing enterocolitis. This is the first case with histologically membranous nephropathy-like findings and marked mesangial proliferation in a child with MIRAGE syndrome with nephrotic syndrome.

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Coproporphyrinogen Oxidase Deficiency Causes Primary Adrenal Insufficiency and 46,XY DSD

Misa Honda, Satoshi Narumi, Kosei Hasegawa, Yoshimitsu Goto, Yusuke Kawashima, Osamu Ohara, Ryuji Fukuzawa, Tomohiro Ishii, Tomonobu Hasegawa

The Journal of Clinical Endocrinology & Metabolism 111 ( 1 ) e83 - e91 2026.01

ISSN 0021972X

Context: Primary adrenal insufficiency (PAI) is a rare, life-threatening condition, and at times is associated with differences of sexual differentiation (DSD). Cytochrome P450 enzymes, which are essential for steroidogenesis in adrenals and gonads, have heme in their active center. CPOX encodes an enzyme coproporphyrinogen oxidase (CPOX) that is involved in the synthesis of heme. Objective: This study aims to report the identification of biallelic inactivating CPOX variants in 3 unrelated patients with PAI and their clinical characteristics. Methods: We report 3 patients with childhood-onset PAI, including 2 with 46,XY DSD. All 3 had adrenal hypoplasia. Additionally, they commonly had severe neonatal jaundice; 2 developed skin blisters in the areas exposed to phototherapy and 2 showed severe neonatal anemia requiring transfusions. Exome sequencing was performed to explore the genetic basis of the patients. The pathogenicity of the identified variants was confirmed with targeted mRNA and proteomic analyses of the patient-derived peripheral blood cells. Results: We identified biallelic rare CPOX variants in each patient, including c.2T > G, p.Arg426*, c.1277G > A, and p.Tyr429Cysfs33*. The 3 patients commonly had the start codon-altering c.2T > G variant. Analysis of the mRNA and proteome of peripheral blood cells from 1 patient (c.2T > G and p.Arg426*) showed that CPOX mRNA expression was comparable to controls; however, CPOX protein expression was significantly decreased to 1%. Conclusion: We provided genetic evidence linking CPOX deficiency and PAI with 46,XY DSD, suggesting that the heme synthesis pathway plays an important role in human steroidogenesis.

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Trends in timing of solid food introduction in Japan between 2014 and 2023: the impact of nutritional policy changes

Sachiko Kaburagi, Tamaki Ito, Shunichiro Nakamura, Erika Nakamura, Tomoyuki Hattori, Takeshi Arimitsu, Munehiro Furuichi, Satoshi Narumi

European Journal of Clinical Nutrition 2026

ISSN 09543007

Following the LEAP and PETIT studies demonstrating that early allergen introduction can prevent food allergies, Japan’s Ministry of Health, Labor and Welfare revised its weaning guideline in 2019. The updated guideline recommended earlier egg introduction and noted that delaying specific foods may increase allergy risk. This study examined trends in the timing of solid food introduction among Japanese infants before and after this revision. We conducted a retrospective analysis using data from the parenting application Papatto Ikuji collected between 2014 and 2023. After excluding outliers and errors, 59,433 infants were analyzed. The age at solid food introduction was examined by birth year. From 2014 to 2018, the age distribution showed two peaks at 5 and 6 months. After 2019, the 6-month peak declined, leaving a single 5-month peak by 2021. These findings suggest that national guideline revisions substantially influenced caregivers’ feeding behaviors, leading to earlier solid food introduction in Japan.

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Machiko Toki, Satoshi Narumi, Junko Hanakawa, Reiko Iwano, Yumi Asakura, Hideaki Ueda, Kenji Kurosawa, Tomonobu Hasegawa, Koji Muroya

Endocrine Journal 73 ( 3 ) 375 - 382 2026

ISSN 09188959

Children with Down syndrome (DS) have a high prevalence of thyroid dysfunction; however, age-related changes in thyroid hormone profiles remain unclear. We investigated the age-related changes in thyroid function in children with DS. We retrospectively analyzed the thyroid function test results of 762 patients with DS aged 3–14 years without known thyroid disease, and compared them with those of 764 age-matched controls with idiopathic short stature. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and the FT3/FT4 ratio were compared between patients with DS with/without congenital heart disease (CHD) and gastrointestinal malformations. In each age group, the log-transformed TSH distribution exhibited similar standard deviation and kurtosis, but showed consistently higher mean values in patients with DS than in controls. Mean FT3 levels were slightly lower in the DS group, except at ages 11–12 years. Mean FT4 levels were slightly lower in the DS group after 9 years of age. The mean FT3/FT4 ratio was lower in the DS group at ages 3–8 years but normalized after 9 years of age. Patients with DS and CHD had higher TSH levels than those without CHD after 11 years of age, whereas FT3, FT4, and the FT3/FT4 ratio showed no significant differences. A rightward shift in serum TSH distribution was observed in patients with DS without thyroid disease, suggesting that TSH levels are generally high in patients with DS. These variations highlight the need for personalized management of thyroid function in patients with DS.

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Mott Cell-Featuring Inflammatory Bowel Disease with DNA Polymerase Epsilon Resolved by Hematopoietic Cell Transplantation

Takeuchi I., Haga C., Fujimori K., Uchiyama T., Kawai T., Tanase-Nakao K., Migita O., Ogawa A., Iguchi A., Shimizu H., Taniguchi K., Matsumoto K., Hata K., Akutsu H., Kato T., Narumi S., Yoshioka T., Ishiguro A., Arai K.

Inflammatory Bowel Diseases 31 ( 12 ) 3465 - 3469 2025.12

ISSN 10780998

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Neurodevelopmental status of children aged 12 to 60 months conceived with artificial oocyte activation in a Cross-Sectional study

Miyazaki K., Yamada M., Akashi K., Jwa S.C., Utsuno H., Kamijo S., Arimitsu T., Hida M., Sato Y., Hirota Y., Narumi S., Tanaka M., Osuga Y., Kuji N.

Scientific Reports 15 ( 1 ) 27547 2025.12

The potential effect of artificial oocyte activation (AOA) following intracytoplasmic sperm injection (ICSI) on neurodevelopment remains uncertain. Since AOA does not fully replicate the physiological Ca²⁺ oscillations essential for fertilization, concerns persist regarding its safety. This study evaluates neurodevelopmental outcomes in children conceived via ICSI-AOA compared to conventional ICSI. A multicentre, cross-sectional study was conducted at Keio University Hospital and eight affiliated institutions, assessing 158 children (ICSI: n = 81, ICSI-AOA: n = 77) aged 12–60 months using the Japanese Ages and Stages Questionnaire, 3rd Edition (J-ASQ-3), covering communication, gross motor, fine motor, problem-solving, and personal-social skills. No significant differences were found in J-ASQ-3 subdomain scores across age groups, and fully adjusted models showed no significant differences in children scoring below the monitoring zone. Subgroup analyses compared differences between AOA protocols (A23187: n = 59; ionomycin: n = 15). AOA protocols were not significantly associated with score variations. Neurodevelopmental outcomes in children conceived via ICSI-AOA were comparable to those conceived via conventional ICSI, suggesting that AOA does not adversely affect early childhood neurodevelopment. These findings support the safety of AOA in assisted reproduction, though further longitudinal research is needed to assess long-term outcomes.

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Optimizing risk stratification in pediatric febrile urinary tract infection: A single-center study in Japan

Tomohiro Inoguchi, Riku Hamada, Yooka Nam, Chikako Terano, Ryoko Harada, Satoshi Narumi, Yuko Hamasaki, Kenji Ishikura, Masataka Honda, Hiroshi Hataya

PLOS One 20 ( 11 November ) e0335743 2025.11

Selecting optimal therapeutic interventions for febrile urinary tract infection (f-UTI) is crucial to prevent complications such as kidney scarring. While current clinical guidelines provide risk-stratified imaging recommendations, they are largely based on Western populations and lack specific predictors for which children will ultimately require therapeutic interventions. This study aimed to establish risk stratification criteria for East Asian children with first-episode f-UTI. This retrospective single-center study analyzed patients aged 2–24 months with first-episode f-UTI. All patients underwent a standardized diagnostic and management protocol, including kidney–bladder ultrasound (KBUS) and voiding cystourethrography (VCUG), to ensure uniform evaluation. The primary outcome was “requirement for therapeutic intervention,” defined as one or more of the following: (1) urological surgery (2) antimicrobial prophylaxis (for vesicoureteral reflux grade ≥III) and (3) antimicrobial treatment for recurrent f-UTI. Multivariate logistic regression was performed to identify independent predictors associated with the interventions. A total of 216 patients were included (median age: 4 months). Overall, 59 patients required therapeutic interventions. Non-Escherichia coli infection (OR 3.3, 95% CI 1.3–8.7) and abnormal KBUS findings (OR 5.3, 95% CI 2.7–10.6) were identified as independent predictors. The sensitivity and specificity of the factors for predicting therapeutic intervention were 64.4% and 73.2%, respectively. This study identified non-E. coli infection and abnormal KBUS findings as key predictors for therapeutic interventions in East Asian children with first-episode f-UTI. These findings suggest that a more targeted approach based on these factors may optimize risk stratification and patient selection for VCUG, improving clinical decision-making.

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Airway compression in a neonate with thyroid dyshormonogenesis due to SLC26A7 defect

Hirano Y., Shimura K., Mitani-Konno M., Fukushima N., Hasegawa T., Narumi S.

European Journal of Endocrinology 193 ( 4 ) K16 - K21 2025.10

ISSN 08044643

SLC26A7 encodes an apical iodide transporter in thyroid follicular cells and causes, when mutated, congenital hypothyroidism (CH). We report a patient diagnosed with goitrous CH, who initially presented with neck enlargement and inspiratory stridor on day 3 of life. Levothyroxine therapy resulted in prompt improvement in upper airway compression, and surgical interventions were avoided. The levothyroxine dosage per body weight was gradually reduced to 0.5 μg/kg/day by age 11 months. Genomic sequencing of CH-related genes identified compound heterozygous protein-truncating SLC26A7 variants: c.612_613dup, p.Ser207Tyrfs*31 and c.1498C>T, p.Gln500*. We emphasize the importance of considering genetic etiologies in cases of neonatal goiter with upper airway compression, particularly in the absence of exposure to excessive iodine or antithyroid drugs

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Three Siblings Born to the Same Mother with Varying Degrees of Strong Positivity for Blocking Type TSH Receptor Antibodies.

Megumi Fujikawa, Kanako Kojima-Ishii, Ken Okamura, Satoshi Narumi, Kanako Tanase-Nakao

Internal medicine (Tokyo, Japan) 2025.09

ISSN 0918-2918

A hypothyroid mother, due to thyroid stimulation-blocking antibody (TSBAb), gave birth three times. Although her TSBAb levels remained almost 100%, her TSH receptor antibody (TRAb) levels before delivery varied as follows: 315.0, 88.2 and 34.9 IU/L in the first, second, and third pregnancies, respectively. The first baby had a hypoplastic thyroid gland and developed severe hypothyroidism three days after birth. The second and third babies only showed latent hypothyroidism. Apparent neonatal hypothyroidism due to maternal TSBAb occurs when TRAb levels are very high, and extremely high TSBAb activity might impair not only the fetal thyroid function, but also its development.

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Post-vaccination fever in infants: Real-world data analysis using a childcare mobile application.

Munehiro Furuichi, Yuki Omoto, Takeshi Arimitsu, Takuma Ohnishi, Takahisa Kimiya, Masayoshi Shinjoh, Tomoyuki Hattori, Satoshi Narumi

Vaccine 62 127551 - 127551 2025.08

ISSN 0264410X

OBJECTIVES: To evaluate the real-world frequency of post-vaccination fever in Japanese infants and to identify factors associated with fever. METHODS: Data on vaccination and daily body temperature were collected using the smartphone application Papatto Ikuji, used by caregivers to record data on their children's daily activities. Mixed-effect logistic regression analysis was conducted to evaluate factors associated with post-vaccination fever. RESULTS: The study included 5690 vaccination events in 2563 infants and toddler aged 2-23 months. Post-vaccination fever was observed most frequently in infants aged 3 months (14.0 %), 4 months (11.6 %), and 12-23 months (9.8 %). Season of vaccination was also a significant factor, with higher fever frequency in summer (9.3 %; odds ratio (OR) 1.59, 95 % confidence interval (CI) 1.16-2.17) compared with winter (6.3 %). A higher fever frequency was observed when PCV13 (13-valent pneumococcal conjugate vaccine), Hib (Haemophilus influenzae type b), and DPT-IPV (Diphtheria, Pertussis, Tetanus, and Inactivated Poliovirus) were administered together (16.8 %; OR 15.40, 95 % CI 6.54-36.26) than vaccination without either of them (1.3 %). CONCLUSIONS: The study identified male, age, vaccine combinations (PCV13 and DPT-IPV), and summer as factors associated with post-vaccination fever in Japanese infants using real-world data from a childcare application.

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Influenza vaccination in Japanese children, 2024/25: Effectiveness of inactivated vaccine and limited use of newly introduced live-attenuated vaccine.

Masayoshi Shinjoh, Kazuyo Tamura, Yoshio Yamaguchi, Hiroyuki Fukushima, Naoki Kuremoto, Maika Tezuka, Naoya Fukushima, Makoto Yoshida, Motoko Shimoyamada, Noriko Suzuki, Ryo Itaki, Michiko Chiga, Ken Kobayashi, Kenichiro Tsunematsu, Mitsuhiro Nishida, Go Yamada, Akimichi Shibata, Atsushi Narabayashi, Akinobu Kamei, Naonori Maeda, Yuki Tsumura, Mizuki Yaginuma, Munehiro Furuichi, Chiharu Kawakami, Satoshi Narumi, Norio Sugaya

Vaccine 61 127429 - 127429 2025.08

ISSN 0264410X

This study evaluated influenza vaccine effectiveness (VE) among children in Japan during the 2024/25 season, when A(H1N1)pdm09 predominated and live-attenuated influenza vaccine (LAIV) was introduced for the first time. Using a test-negative design, febrile children aged 6 months to 15 years were enrolled from 16 hospitals and 2 clinics. Among 1351 participants, LAIV coverage was low (1.2 %), limiting its VE assessment. In contrast, inactivated influenza vaccine (IIV) coverage was 35 %. The adjusted VE of IIV against influenza A was 73 % (95 % CI: 57-83 %) in inpatients and 57 % (24-75 %) in outpatients. VE was significant in younger age groups. A two-dose regimen provided no additional benefit. The effectiveness observed was consistent with previous seasons and global estimates. While the effectiveness of LAIV was unevaluable due to low coverage, IIV remained effective, supporting its continued use in pediatric populations. LAIV effectiveness should be re-evaluated if coverage increases.

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Genetic and Clinical Characteristics of 185 Japanese Children With 46,XY Differences of Sex Development

Mie Hayashi, Satoshi Narumi, Takeshi Sato, Naoko Amano, Ayuko Suzuki Suwanai, Hidenori Haruna, Koji Muroya, Masanori Adachi, Hiroshi Asanuma, Hirofumi Ohashi, Tomohiro Ishii, Tomonobu Hasegawa

The Journal of Clinical Endocrinology & Metabolism 110 ( 8 ) e2682 - e2690 2025.08

ISSN 0021972X

Context 46,XY differences of sex development (DSD) are heterogeneous in etiology. The detailed phenotypes of 46,XY DSD patients with monogenic disorders have not been fully elucidated. Objectives To estimate the proportion of monogenic disorders in 46,XY DSD and to characterize the clinical phenotypes of patients with monogenic disorders. Methods A total of 185 Japanese patients (178 families) were enrolled. We sequenced 25 genes related to 46,XY DSD and assessed the pathogenicity of the identified sequence variants according to the American College of Medical Genetics and Genomics guidelines, supplemented by in silico and/or in vitro analyses. We analyzed the clinical phenotypes of patients with monogenic disorders, with particular attention to the external or internal genitalia. Results We identified 51 patients (47 families) with any monogenic disorders (26%), who possessed pathogenic variants in AR (11%), SRD5A2 (4.5%), NR5A1 (4.0%), SRY (2.8%), WT1 (1.1%), STAR (1.1%), CYP17A1 (0.56%), HSD3B2 (0.56%), or MAP3K1 (0.56%). The proportion of monogenic disorders was significantly higher in subjects with detected Müllerian derivatives (57%) than in those undetected (26%) (P =. 029), and in subjects with female-typical genitalia (91%) than in those with ambiguous genitalia (19%) (P <. 001). Conclusion The proportion of monogenic disorders in Japanese 46,XY DSD patients was approximately 26%. Monogenic disorders were frequent among patients with severe undermasculinization of the external or internal genitalia.

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Clinical and Genetic Characteristics of Adult Nonautoimmune Hypothyroidism: A Single-institution Study.

Chiho Sugisawa, Erika Uehara, Kanako Tanase-Nakao, Kosuke Inoue, Tatsuya Iida, Fumiko Otsuka, Nami Suzuki, Hidemi Ohye, Miho Fukushita, Masako Matsumoto, Ai Yoshihara, Natsuko Watanabe, Kiminori Sugino, Jaeduk Yoshimura Noh, Matsuo Taniyama, Satoshi Narumi, Koichi Ito

The Journal of clinical endocrinology and metabolism 111 ( 1 ) e32 - e40 2025.06

ISSN 0021-972X

PURPOSE: Nonautoimmune hypothyroidism is characterized by hypothyroidism and negative thyroid autoantibodies with limited knowledge of its clinical and genetic characteristics. The aim was to characterize the clinical and genetic features of nonautoimmune hypothyroidism. METHODS: This retrospective study included 1470 treatment-naive adult hypothyroid patients (serum TSH >10 mU/L) born before 1979 and were followed up at Ito Hospital, Tokyo, Japan. Of these, 220 patients were diagnosed with idiopathic nonautoimmune hypothyroidism by thyroid autoantibody measurements. Sequencing of 13 genes associated with nonautoimmune hypothyroidism was performed of 101 of the 220 patients. Clinical characteristics, including thyroid function and morphology, were systematically evaluated. RESULTS: The proportion of idiopathic nonautoimmune hypothyroidism among the 1470 patients with treatment-naive nontransient hypothyroidism was 15.0%. Idiopathic nonautoimmune hypothyroidism patients had lower serum TSH (17.0 vs 28.3 mU/L; P < .001), higher serum fT4 (11.5 vs 8.9 pmol/L; P < .001), and a smaller thyroid volume (13.4 vs 24.9 g; P < .001) than autoimmune hypothyroidism patients. Genetic analysis showed that 5.0% of the analyzed idiopathic nonautoimmune hypothyroidism patients had a Mendelian disorder, with PAX8 being the most commonly affected gene. An additional 19% of the analyzed patients carried monoallelic variants in hypothyroidism-associated genes, such as DUOX2, DUOXA2, SLC26A4, TG, TPO, and TSHR, that cause autosomal recessive genetic defects. CONCLUSION: In patients with treatment-naive adult nonautoimmune hypothyroidism, thyroid dysfunction was milder and thyroid volume was smaller than in patients with autoimmune hypothyroidism. Mendelian forms were rare, but the unexpectedly high frequency of monoallelic variant carriers suggests that these variants may confer genetic risk for nonautoimmune hypothyroidism.

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Reference Values of Arm Span and Arm Span to Height Ratio of Japanese Population in Childhood and Adolescence: Comparison With Dutch and Turkish Population

Hirano Y., Inokuchi M., Narumi S., Hasegawa T.

American Journal of Human Biology 37 ( 4 ) e70051 2025.04

ISSN 10420533

Objectives: To establish age-specific reference values for the arm span and arm span/height ratio of the Japanese population in children and adolescence and elucidate their characteristics compared with those of other populations. Study Design: We analyzed data from a national survey on the body sizes of Japanese people conducted between 1992 and 1994 by the Research Institute of Human Engineering for Quality Life. This study was an observational cross-sectional study, including 6089 boys and 4970 girls aged between 5.5 and 18.5 years. We constructed the reference values and delineated the reference curves for the arm span and arm span/height ratio of the Japanese population in childhood and adolescence using the LMS method. The references were compared with those of the Dutch and Turkish populations using the reference curve of 0 standard deviation. Results: The arm span of the Japanese population increased throughout childhood, with a particularly large increase at the age of puberty. The arm span/height ratio also increased slowly throughout childhood. The Japanese population had a smaller arm span/height ratio than the Dutch and Turkish populations of all ages in childhood and adolescence. Moreover, the arm span/height ratio of the Japanese population reached a constant value at an earlier age than in the Dutch and Turkish populations. Conclusions: We constructed the first reference values for the arm span of Japanese children and adolescents. The Japanese population has shorter arm lengths in relation to their height, and their arm span/height ratio reaches a constant value at an earlier age, compared with the Dutch and Turkish populations.

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Familial Non-Autoimmune Hyperthyroidism Caused by an Extracellular Domain Variant (p.Leu267Phe) of the TSH Receptor.

Shimura K, Ichihashi Y, Abe K, Ishii T, Hasegawa T, Narumi S

Hormone research in paediatrics 1 - 9 2025.02

ISSN 1663-2818

Introduction: Non-autoimmune hyperthyroidism (NAH) is a rare genetic disorder caused by germline-activating variants in the TSH receptor (TSHR) gene. While most NAH-related TSHR variants are located in the seven-transmembrane domain (7TMD), three variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) have been identified in the extracellular domain (ECD), with p.Leu267Phe previously not showing constitutively active in vitro. Methods: We searched for TSHR variants in a Japanese family with NAH using PCR-based direct sequencing. We created three ECD variants (p.Leu267Phe, p.Ser281Asn, and p.Asn406Ser) and a series of variants in which Leu267 was mutated to 18 amino acids other than Leu and Phe. Based on the cryo-electron microscopic structures, we evaluated the structure-function relationship of TSHR. We compared their cAMP-producing capacities to WT-TSHR in the luciferase activity assay using HEK293 cells. Western blot and fluorescence immunostaining were performed using HA-tagged TSHR vectors to compare Leu267Phe-TSHR with WT-TSHR. Results: A heterozygous TSHR variant (p.Leu267Phe) was identified. Comparison of the cryo-electron microscopy structures of the activated and inactivated TSHRs revealed a significant change in the ECD structure around Leu<sup>267</sup>. The ligand-independent cAMP-producing capacities compared to WT-TSHR were 238 ± 20% (mean ± SEM) for Leu267Phe. Of all 19 possible variants created through systematic mutagenesis, only Leu267Phe-TSHR and Leu267Tyr-TSHR exhibited significantly higher ligand-independent cAMP-producing capacities. Immunoblotting and fluorescence immunostaining showed that the Leu267Phe variant did not affect protein expression levels and intracellular localization of TSHR. Discussion/Conclusion: Leu267Phe-TSHR causes NAH. Substituting Leu<sup>267</sup> to aromatic amino acids may shift the equilibrium of the TSHR state toward activation.

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スマートフォンアプリによるビッグデータから分かる乳児期の睡眠習慣形成

小川恵梨, 小林久人, 服部伴之, 古市宗弘, 有光威志, 鳴海覚志

日本小児科学会雑誌 ((公社)日本小児科学会) 129 ( 2 ) 195 - 195 2025.02

ISSN 0001-6543

Recovery from Atrophic Autoimmune Thyroiditis in a Child: Thyroid Stimulation-Blocking Antibody as a Prognostic Marker.

Kusano C, Hori N, Hasegawa T, Narumi S

Hormone research in paediatrics 1 - 5 2025.01

ISSN 1663-2818

Introduction: Atrophic autoimmune thyroiditis (AAT) is a form of autoimmune hypothyroidism characterized by the absence of a goiter. Thyroid stimulation-blocking antibody (TSBAb) has been detected in a subset of pediatric AAT cases. Although the disappearance of TSBAb has been related with the recovery of thyroid function in adult AAT cases, similar outcomes have not been documented in pediatric cases. Case Presentation: A 2-year-old Japanese boy presented for evaluation of stunted growth from1 year 10 months of age. Tests for congenital hypothyroidism were negative on newborn screening, and he had no significant medical history. However, he showed symptoms of hypothyroidism (inactiveness, hair loss, dry skin), and primary hypothyroidism was confirmed by blood test (serum TSH level, 818 mU/L; serum free T4 level, <0.40 ng/ dL). The patient exhibited a unique antibody profile: positive for TSH receptor antibody (TRAb) and TSBAb and negative for anti-thyroglobulin antibody (TgAb) and antiperoxidase antibody (TPOAb). He was treated with levothyroxine, after which his growth was normalized. During the 8-year follow-up, the patient's TSBAb levels decreased, allowing for the discontinuation of levothyroxine therapy. Conclusion: We reported the case of a 2-year-old boy diagnosed with AAT who presented with a characteristic antibody profile, negative for TgAb and TPOAb, but positive for TRAb and TSBAb. During 8 years of follow-up, TSBAb seroconversion to negative was observed, leading to treatment discontinuation at age 10 years. This case suggests that monitoring of TSBAb after a diagnosis of AAT may be used to determine treatment discontinuation even in children.

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Sex education to an adolescent male with Down syndrome in a single-mother family in Japan.

Amuna Saito, Takeshi Sato, Haruko Shima, Hiroyuki Yamagishi, Satoshi Narumi, Tomohiro Ishii, Tomonobu Hasegawa

Pediatrics international : official journal of the Japan Pediatric Society 67 ( 1 ) e15896 2025.01

ISSN 13288067

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Toyoko Kids: A case series on the psychosocial backgrounds of eight runaway girls transported to emergency care in Tokyo

Nakamura S., Baba T., Tokita N., Shimizu C., Yamamoto R., Narumi S.

Pediatrics International 67 ( 1 ) e70248 2025.01

ISSN 13288067

Aim: Runaway behavior, defined as leaving home without parental permission and not returning, is associated with adverse educational, physical, and mental health outcomes. In Japan, since around 2018, a group of runaway adolescents known as “Toyoko Kids” has emerged in Tokyo's Kabukicho area, reportedly engaging in substance use, violence, and prostitution. This study aimed to examine the psychosocial characteristics of Toyoko Kids who were transported to emergency care due to impaired consciousness from drug overdose or alcohol intoxication. Methods: We conducted a retrospective chart review of eight female adolescents under 18 years old, transported from Kabukicho to Keio University Hospital between June 2022 and August 2023. Inclusion criteria included having run away for at least two nights (or one night for those under 15) and being transported by a third party. A multidisciplinary team assessed psychosocial risks using a Bio-Psycho-Social model. Data on consciousness level, pregnancy, substance use, self-harm, psychiatric history, family structure, school attendance, abuse, and child welfare involvement were analyzed and compared with national statistics. Results: All subjects were female, aged 12–16. The most common reason for transport was impaired consciousness due to overdose, primarily involving over-the-counter medications. Self-harm was confirmed in 86% and abuse in 67% of cases. Although several had prior psychiatric or welfare intervention, support was often temporary and insufficient. Most came from single-parent households, and over half had a history of school absenteeism. Conclusions: This study identified severe psychosocial vulnerabilities among Toyoko Kids. Findings highlight gaps in mental health and child protection systems.

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