Clinical Pediatric Endocrinology
Online ISSN : 1347-7358
Print ISSN : 0918-5739
ISSN-L : 0918-5739
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JSPE International Prize
  • Francesco Chiarelli, Cosimo Giannini, Marina Primavera
    2019 Volume 28 Issue 3 Pages 43-57
    Published: 2019
    Released: July 20, 2019
    JOURNALS FREE ACCESS

    Type 1 diabetes (T1D) is a chronic T-cell mediated autoimmune disease characterized by destruction of beta cells. Although new data have better defined the complex etiology underling the interrelation of genetic and environmental factors in the natural history of T1D, relevant pieces of the puzzle still are missing. Genetic predisposition is mainly associated to some histocompatibility leukocyte antigen (HLA) alleles; however, recent data suggest that new as well as still unknown genes might better define the complex multigenetic risk of the disease. In addition to the genetic effects, the concordance in familial aggregation in T1D indicates a pivotal role of environmental factors in the course of the disease, facilitating autoantibodies production. JDRF has recently proposed a new early stage of T1D according to which the detection of two or more autoantibodies in the blood, might describe those children at increased risk of developing T1D during the following years. In contrast to the improvements reached by prediction models, to date primary, secondary and tertiary prevention have still failed to achieve a safe and efficacious intervention strategies. Anyway, the most recent progresses in this field pave the way for future studies, with the aim of preventing T1D in children.

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Review
  • Kenji Ihara
    2019 Volume 28 Issue 3 Pages 59-68
    Published: 2019
    Released: July 20, 2019
    JOURNALS FREE ACCESS

    In recent years, immune checkpoint inhibitor therapy has attracted a great deal of attention in the field of cancer treatment. In the clinical setting, antibodies targeting programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have been successfully used to treat adult patients with various types of intractable cancer. However, in a substantial number of patients, ICI therapy is associated with autoimmune toxicities known as immune-related adverse events (IRAEs). Endocrinopathies, such as hypophysitis or autoimmune thyroid disease, may occur and can present unique clinical features that have not been documented with traditional chemotherapies. A Japanese clinical trial evaluating the anti-PD-1 antibody nivolumab for the treatment of pediatric patients with refractory malignant solid tumors and Hodgkin lymphoma has been ongoing since 2017. Moreover, tumors associated with Lynch syndrome, a hereditary form of mismatch repair deficiency, are being focused and represent the next target for ICI therapy in Japan. For the safe management of pediatric cancer patients treated with ICIs, pediatric endocrinologists must be aware of the risk of autoimmune endocrinopathies and perform relevant screening tests at appropriate stages of growth and development.

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  • Toshihiro Tajima, Akie Nakamura, Makiko Oguma, Masayo Yamazaki
    2019 Volume 28 Issue 3 Pages 69-79
    Published: 2019
    Released: July 20, 2019
    JOURNALS FREE ACCESS

    Congenital central hypothyroidism (C-CH) is caused by defects in the secretion of thyrotropin-releasing hormone (TRH) and/or TSH, leading to an impairment in the release of hormones from the thyroid. The causes of C-CH include congenital anomalies of the hypothalamic-pituitary regions and several genetic defects. In terms of endocrinology, C-CH is divided into two categories: (1) accompanied by another pituitary hormone deficiency and called combined pituitary hormone deficiency, and (2) isolated C-CH, showing mainly TSH deficiency. For isolated C-CH, a mutation in the TSH gene (TSHB) encoding the β-subunit of the protein was first found in 1990 by Japanese researchers, and thereafter several mutations in TSHB have been reported. Mutations in the thyrotropin-releasing hormone receptor gene (TRHR), as well as genetic defects in immunoglobulin superfamily 1 (IGSF1), have also been identified. It was recently found that isolated C-CH is caused by mutations in transducin β-like 1 X-linked and insulin receptor substrate 4. It is noted that all patients with TSHB deficiency and some with IGSF1 deficiency show severe hypothyroidism soon after birth. Among the causes of C-CH, high frequency of mutations in IGSF1 is the most prevalent. This review focuses on recent findings on isolated C-CH.

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Original Article
  • Yasuaki Saijo, Yoshiya Ito, Eiji Yoshioka, Yukihiro Sato, Machiko Mina ...
    2019 Volume 28 Issue 3 Pages 81-89
    Published: 2019
    Released: July 20, 2019
    JOURNALS FREE ACCESS

    This study aimed to construct a childhood obesity risk index based on predictors identified in pregnant women and 1-yr-old infants. The primary outcome was an identified obesity index of > 20% at 6–8 yr of age. Of a total sample size of 6,846 mother-child pairs, 80% and 20% were randomly allocated to the derivation and validation cohorts, respectively. For the derivation cohort, univariate and multivariate logistic regression analyses of data were conducted to identify the final predictors to determine the childhood obesity risk score algorithm. These included pre-pregnancy body mass index (BMI), child’s gender, smoking during pregnancy, education, and obesity index at one yr of age. The β coefficients for categories of predictor variables were each divided by the smallest value among them. The quotient was rounded off to the integer and assigned to the risk score, and a value of zero was assigned to reference categories. A total risk score was calculated for each individual. A cutoff point ≥ 16 had 22.2% and 21.8% positive predictive values in the derivation and validation cohorts, respectively. In conclusion, the childhood obesity risk score algorithm was constructed based on generic predictors that can be easily obtained from maternal and child health handbooks.

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Case Report
  • Tomohiro Hori, Hidenori Ohnishi, Tomonori Kadowaki, Norio Kawamoto, Hi ...
    2019 Volume 28 Issue 3 Pages 91-96
    Published: 2019
    Released: July 20, 2019
    JOURNALS FREE ACCESS

    Hashimoto’s thyroiditis (HT) is an autoimmune disease thought to involve a combination of genetic and environmental factors, but its detailed pathogenesis is unknown. We present a family with haploinsufficiency of the gene encoding tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) and show a link with HT in a three-generation pedigree. Currently, TNFAIP3 polymorphisms are associated with several autoimmune diseases, and haploinsufficiency of A20 was recently observed in families with an early-onset autoinflammatory disease resembling Behçet’s disease. However, HT has not been linked with TNFAIP3 variants. We analyzed TNFAIP3 and human leukocyte antigen (HLA) in the family showing HT as an autosomal dominant trait, and identified a novel heterozygous c.2209delC mutation of TNFAIP3 in the members with HT. The known HLA haplotypes linked to HT could not be identified. Based on our analysis of this pedigree, we consider HT as a possible phenotype of A20 haploinsufficiency.

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