Tanaka Growth Clinic

Tokyo, Japan

Tanaka Growth Clinic

Tokyo, Japan
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Martin D.D.,University of Tübingen | Sato K.,Tohoku University | Sato M.,Toho University | Tanaka T.,Tanaka Growth Clinic
Hormone Research in Paediatrics | Year: 2010

BoneXpert, an automated method for analysis of hand radiographs of children, has recently been developed and validated in European children. It determines Tanner-Whitehouse (TW) and Greulich Pyle (GP) bone ages (BA). The purpose of this work is to validate BoneXpert BA in Japanese children and determine the following two properties of the method: (1) The accuracy of the BA, i.e. the standard deviation from an experienced Japanese TW BA rater. (2) The precision of the BA, i.e. BoneXpert's ability to yield the same BA value on a repeated radiograph. The data consist of two studies: 185 radiographs of 22 normal children followed longitudinally from approximately 7 years to full maturity, and 284 radiographs of 22 patients with growth hormone deficiency treated with growth hormone and gonadotropin-releasing hormone analogue followed from an age of 4-11 years to almost full maturity. All radiographs were rated manually according to the TW-Japan system. BoneXpert processed all images, and the accuracy (SD) of TW-Japan BA was 0.72 years (95% CI 0.68-0.76). The precision error (SD) on a single determination of GP BA was 0.17 years (95% CI 0.15-0.19). It is concluded that BoneXpert performs as well in Japanese children as it does in Caucasian children. This study accomplishes a calibration of BoneXpert to the TW-Japan standard, which performs well for the entire BA range from 4 years up to full maturity. © 2010 S. Karger AG.


Kato N.,Japan National Institute of Public Health | Takimoto H.,National Institute of Health and Nutrition | Yokoyama T.,Japan National Institute of Public Health | Yokoya S.,National Center for Child Health and Development | And 2 more authors.
Acta Paediatrica, International Journal of Paediatrics | Year: 2014

Aim To provide updated growth references for Japanese children from birth to 6 years of age, for use in both growth monitoring and child care. Methods We analysed data from two national representative surveys that provided cross-sectional data on 3000 areas in the 2005 national census and longitudinal data from 136 hospitals. Growth references for length/height, weight, head circumference and chest circumference were constructed using the lambda-mu-sigma (LMS) method, with estimates of the L, M and S parameters. These updated values were then compared with growth references published by the World Health Organization. Results The 3rd, 50th and 97th smoothed percentile values of length/height, weight, head circumference and chest circumference for boys and girls from birth to 6 years are presented. The comparisons show some large differences in median measurements between the charts. Conclusion Our growth references are based on a current, nationally representative sample of Japanese children. The results provide deep insight into child growth from a historical, ethnic and environmental point of view. © 2014 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.


Kappelgaard A.-M.,Novo Nordisk AS | Kiyomi F.,Novo Nordisk AS | Horikawa R.,National Center for Child Health and Development | Yokoya S.,National Center for Child Health and Development | Tanaka T.,Tanaka Growth Clinic
Hormone Research in Paediatrics | Year: 2014

Background/Aims: An examination of the effects of up to 260 weeks of growth hormone (GH) therapy on metabolic parameters in Japanese children born small for gestational age (SGA). Methods: Data were analysed from a 156-week extension of a 104-week multicentre, randomised, double-blind, parallel-group trial. Sixty-five children born SGA (age 3-<8 years) received 33 μg/kg/day (n = 31, 64.5% male) or 67 μg/kg/day (n = 34, 58.8% male) GH for 260 weeks. Changes in metabolic parameters - glucose, insulin, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol - were recorded. Alterations in weight, body mass index standard deviation score (BMI SDS) and vital signs were also evaluated. Results: Over 260 weeks of GH treatment, a positive correlation between Δheight SDS and Δinsulin-like growth factor-I SDS was observed. Insulin and glucose levels were generally unaffected. Favourable changes in lipid profiles were recorded, which were maintained for the study duration. No adverse alterations in weight, BMI SDS or vital signs were noted. Conclusion: Long-term, continuous GH treatment in children born SGA appears to be efficacious, associated with potential benefits for several metabolic parameters and associated with no long-term safety concerns. © 2014 S. Karger AG, Basel.


Amano N.,Keio University | Mukai T.,Asahikawa Kosei General Hospital | Ito Y.,Japanese Red Cross Hokkaido College of Nursing | Narumi S.,Keio University | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: C-type natriuretic peptide-natriuretic peptide receptor B (NPR-B) signaling is critical for endochondral ossification, which is responsible for longitudinal growth in limbs and vertebrae. Biallelic NPR2 mutations cause acromesomelic dysplasia, type Maroteaux, which is bone dysplasia characterized by severe short stature and short limbs. A monoallelic NPR2 mutation has been suggested to mildly impair long bone growth. Objective: The goal of this study was to identify and characterize NPR2 mutations among Japanese patients with short stature. Subjects and Methods: We enrolled 101 unrelated Japanese patients with short stature. NPR2 and NPPC were sequenced, and the identified variants were characterized in vitro. Results: In two subjects,weidentified two novel heterozygous NPR2 mutations (R110C and Q417E) causing a loss of C-type natriuretic peptide-dependent cGMP generation capacities and having dominant-negative effects. R110C was defective in trafficking from the endoplasmic reticulum to the Golgi apparatus. In contrast, Q417E showed clear cell surface expression. Conclusions: We identified heterozygous NPR2 mutations in 2% of Japanese patients with short stature. Our in vitro findings indicate that NPR2 mutations have a dominant negative effect, and their dominant-negative mechanisms vary corresponding to the molecular pathogenesis of the mutations. Copyright © 2014 by the Endocrine Society.


Tanaka T.,Tanaka Growth Clinic
Pediatric Endocrinology Reviews | Year: 2012

Growth hormone (GH) treatment was approved for growth hormone deficiency (GHD) in Japan in 1975. Since then, GH treatment has been approved for treating five other diseases with short stature. However, available data on adult height after long-term GH treatment is limited to patients with GHD and Turner syndrome. Although adult height of patients with GHD has improved with early diagnosis and early initiation of treatment, the adult height after long-term GH treatment is still not so satisfactory because the therapeutic dose used in Japan is smaller than that used in US and Europe. With early diagnosis, early high-dose treatment, and low-dose estrogen replacement therapy, both adult height and quality of life (QOL) of the patients with Turner syndrome have been improved.


Shimatsu A.,National Hospital Organization Kyoto Medical Center | Tai S.,Tai Clinic | Tai S.,Eli Lilly and Company | Tanaka T.,Tanaka Growth Clinic | And 3 more authors.
Endocrine Journal | Year: 2011

The clinical characteristics of Caucasian adults with growth hormone (GH) deficiency (GHD) have been well defined. However, no large-scale clinical practice study has examined the clinical characteristics of Japanese adults with GHD. The aim of our study was to describe the clinical characteristics of Japanese adults with GHD by reviewing the records of participants who were GH-naive at the time of enrollment in the Hypopituitary Control and Complications Study (N = 349). The majority of participants (280 of 349; 80.2%) had adult-onset rather than childhood-onset GHD. Hypothalamo-pituitary tumors were the most common cause of GHD in Japanese adults (247 of 349; 70.8%); these tumors were primarily pituitary adenomas in participants with adult-onset GHD (156 of 243; 64.2%), and germ cell tumors (19 of 40; 47.5%) and craniopharyngiomas (18 of 40; 45.0%) in participants with childhood-onset GHD. Most participants (310 of 349; 88.8%) had multiple pituitary hormone deficiencies. Dyslipidemia (195 of 349; 55.9%), visual field loss (67 of 349; 19.2%), hypertension (59 of 349; 16.9%), and liver disease (54 of 349; 15.5%) were the most common pre-existing conditions in Japanese adults with GHD. Quality of life was decreased in seven of the eight short form-36 domains in participants with GHD compared with age- and sex-matched healthy Japanese individuals. Our findings confirm that the clinical characteristics of Japanese adults with GHD are similar to those of Caucasian adults with GHD. Confirmation of these clinical characteristics will enhance the ability of clinicians to identify and treat Japanese adults with GHD. © The Japan Endocrine Society.


Ranke M.B.,University Hospital of Tuebingen | Lindberg A.,Pfizer | Mullis P.E.,University of Bern | Geffner M.E.,Childrens Hospital Los Angeles | And 4 more authors.
Hormone Research in Paediatrics | Year: 2013

Treatment with growth hormone (GH) has become standard practice for replacement in GH-deficient children or pharmacotherapy in a variety of disorders with short stature. However, even today, the reported adult heights achieved often remain below the normal range. In addition, the treatment is expensive and may be associated with long-term risks. Thus, a discussion of the factors relevant for achieving an optimal individual outcome in terms of growth, costs, and risks is required. In the present review, the heterogenous approaches of treatment with GH are discussed, considering the parameters available for an evaluation of the short- and long-term outcomes at different stages of treatment. This discourse introduces the potential of the newly emerging prediction algorithms in comparison to other more conventional approaches for the planning and evaluation of the response to GH. In rare disorders such as those with short stature, treatment decisions cannot easily be deduced from personal experience. An interactive approach utilizing the derived experience from large cohorts for the evaluation of the individual patient and the required decision-making may facilitate the use of GH. Such an approach should also lead to avoiding unnecessary long-term treatment in unresponsive individuals. Copyright © 2013 S. Karger AG, Basel.


Tanaka T.,Tanaka Growth Clinic | Naiki Y.,National Center for Child Health and Development | Horikawa R.,National Center for Child Health and Development
Clinical Pediatric Endocrinology | Year: 2012

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone. © 2012 by The Japanese Society for Pediatric Endocrinology.


PubMed | National Center for Child Health and Development, Novo Nordisk AS and Tanaka Growth Clinic
Type: | Journal: International journal of pediatric endocrinology | Year: 2016

Long-term growth hormone (GH) treatments in short children born small for gestational age (SGA) restore lipid metabolism, but also increase insulin resistance. The aim of this study was to evaluate the influence of long-term GH therapy on lipid and glucose metabolism as well as its dose dependency in short Japanese children born SGA.Eighty Japanese children with a short stature who were born SGA participated in this study; 65 were treated with fixed GH doses of 0.033 (low) or 0.067 (high) mg/kg/day for 260weeks; 15 were untreated controls in the first year and were randomized to one of the two treatment groups at week 52. Serum cholesterol, glucose and insulin levels were regularly measured. An oral glucose tolerance test (OGTT) was conducted annually.The mean age at the start of GH therapy was approximately 5.3years. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the high dose group significantly decreased over time during GH therapy. In both dose groups for TC, and in the high dose group for LDL-C, the higher the baseline values, the greater the decrease after 260weeks. The rate of the decrease observed after 260weeks in patients with high LDL-C levels was greater in the high dose group. Based on the results of OGTT, no patient was classified as being diabetic; however, annual increases were observed in post-OGTT insulin levels. After 260weeks, the homeostasis model assessment as an index of insulin resistance (HOMA-IR) increased, suggesting that insulin resistance developed over time with the GH treatment, while 36.6% of the subjects entered puberty.Long-term continuous GH treatment for children born SGA may have a potentially beneficial effect on several parameters in lipid metabolism and does not adversely affect glucose metabolism.GHLIQUID-1516, GHLIQUID-1517, Japan Pharmaceutical Information Center Clinical trial registration: JapicCTI-050132. Registered 13 September 2005. Retrospectively registered. JapicCTI-050137. Registered 13 September 2005. Retrospectively registered. ClinicalTrials.gov trial registration: NCT00184717. Registered 13 September 2005. Retrospectively registered.


PubMed | Hamamatsu University School of Medicine, Aichi Childrens Health and Medical Center, Niigata University, Kanagawa Childrens Medical Center and 14 more.
Type: Journal Article | Journal: Journal of human genetics | Year: 2016

The etiology of idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD) in European patients is known to include SHOX mutations and copy-number variations (CNVs) involving SHOX and/or the highly evolutionarily conserved non-coding DNA elements (CNEs) flanking the gene. However, the frequency and types of SHOX abnormalities in non-European patients and the clinical importance of mutations in the CNEs remains to be clarified. Here, we performed systematic molecular analyses of SHOX for 328 Japanese patients with ISS or LWD. SHOX abnormalities accounted for 3.8% of ISS and 50% of LWD cases. CNVs around SHOX were identified in 16 cases, although the ~47kb deletion frequently reported in European patients was absent in our cases. Probably damaging mutations and benign/silent substitutions were detected in four cases, respectively. Although CNE-linked substitutions were detected in 15 cases, most of them affected poorly conserved nucleotides and were shared by unaffected individuals. These results suggest that the frequency and mutation spectrum of SHOX abnormalities are comparable between Asian and European patients, with the exception of a European-specific downstream deletion. Furthermore, this study highlights the clinical importance and genetic heterogeneity of the SHOX-flanking CNVs, and indicates a limited clinical significance of point mutations in the CNEs.

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