Very young children with Prader-Willi syndrome are refractory to growth hormone-associated decreases in free thyroxine levels.

The earlier initiation of growth hormone (GH) treatment for patients with Prader-Willi syndrome (PWS) who are younger than 2 years has become more prevalent. Because free thyroxine (FT4) levels are low during this period, GH may induce further reductions; however, limited information is currently available on this issue. Therefore, we herein performed age-dependent and time-course analyses of thyroid hormone levels in GH-treated PWS children. This retrospective analysis included genetically diagnosed PWS patients (N = 37, median age of 26 months). An age-dependent analysis was performed by subdividing subjects based on age [a younger group aged between 1 and 24 months (N = 16) and an older group between 25 and 84 months (N = 21)] and was followed by a multiple regression analysis with adjustments for sex and the cumulative GH dose per bodyweight. A time-course analysis of subjects who had not received levothyroxine during the first 18 months of GH treatment (N = 28) was conducted. A one-month treatment with GH decreased FT4 levels in the older group, but not in the younger group, and this was associated with increases in thyroid-stimulating hormone levels. A positive correlation was noted between age and decreases in FT4 levels independent of the cumulative GH dose per bodyweight. The time-course analysis revealed no changes in FT4 levels in the younger group, while transient decreases were observed in the older group. In conclusion, GH treatment causes age-dependent changes in FT4 levels. This result will help clinicians establish a therapeutic strategy to decide the necessity of levothyroxine supplementation in GH-treated children with PWS.

Dosage of hydrocortisone during late infancy is positively associated with changes in body mass index during early childhood in patients with 21-hydroxylase deficiency.

Obesity is a major complication in children with 21-hydroxylase deficiency (21-OHD). There is evidence to show that higher body mass index (BMI) during infancy and early childhood is associated with an increased risk for the subsequent development of obesity in the general population; however, limited information is currently available on this issue in 21-OHD patients. Additionally, despite the frequent use of supraphysiological dosages of hydrocortisone in 21-OHD, the association between BMI and hydrocortisone dosage during these periods remains largely unclear; therefore, we retrospectively investigated BMI at approximately 1 and 3 years old and its association with hydrocortisone dosage in 56 children with 21-OHD. The median BMI-standard deviation score (SDS) was 0.28 (Interquartile range [IQR]: -0.53 to 1.09) and 0.39 (IQR: -0.44 to 1.14) at approximately 1 and 3 years old, respectively, and no association was observed between hydrocortisone dosage and BMI-SDS at either time-point; however, multivariate analysis revealed that hydrocortisone dosage at approximately 1 year old was positively associated with changes in BMI (ß = 0.57, p = 0.013) and BMI-SDS (ß = 0.59, p = 0.011) between approximately 1 and 3 years old after adjustment for age, sex, and changes in hydrocortisone dosage during the same period. The average dosage of hydrocortisone between approximately 6 months and 1 year old also showed similar results. These results indicate that a higher dosage of hydrocortisone during late infancy is associated with a higher BMI at approximately 3 years old, which may lead to the development of obesity later in life in children with 21-OHD.

Circulating insulin-like growth factor 1 levels are reduced in very young children with Prader-Willi syndrome independent of anthropometric parameters and nutritional status.

OBJECTIVE: Insulin growth factor-1 (IGF-1) is used to evaluate growth hormone (GH) sufficiency and is decreased in children with Prader-Willi syndrome (PWS). Although IGF-1 is negatively affected by body size and nutritional status, both of which are impaired in PWS children, these variables are typically not considered when assessing IGF-1 levels in these subjects. Here, we compared IGF-1 levels in PWS children to controls matched for age, sex, anthropometric parameters, and nutritional status. DESIGN/PATIENTS/MEASUREMENTS: The retrospective analysis included genetically diagnosed PWS subjects (n = 65, median age; 14.0 months) and controls (n = 111, 14.3 months) matched for age, sex, anthropometric parameters (height-standard deviation score [SDS], weight-SDS, body mass index-SDS), and serum albumin levels, a marker for nutritional status. IGF-1 SDS was compared between PWS subjects and controls after adjustment for confounding variables. The GH provocation test was performed in 29 PWS subjects, and IGF-1 SDS was compared between GH-sufficient (n = 20) and GH-deficient (n = 9) subjects. Spearman's rank correlation coefficient was performed to investigate the association between age and IGF-1 SDS. None had received GH or levothyroxine treatment. RESULTS: After adjustment for confounding variables, IGF-1 SDS was significantly lower in PWS subjects than controls (-1.56 vs. -1.01, p = .003), while it was not different between GH-sufficient and GH-deficient PWS subjects. Correlation analysis failed to show an association between age and IGF-1 SDS both in control and PWS groups. CONCLUSIONS: IGF-1 SDS is lower in very young children with PWS independent of anthropometric parameters and nutritional status, suggesting the presence of hypothalamic dysfunction of GH secretion.

Current status of transition medicine for 21-hydroxylase deficiency in Japan: from the perspective of pediatric endocrinologists.

To manage of 21-hydroxylase deficiency (21-OHD), transition medicine from pediatric to adult health care is an important process and requires individually optimized approaches. We sent cross-sectional questionnaire surveys on the current status of transition from pediatric to adult health care in 21-OHD patients to all councillors of the Japanese Society for Pediatric Endocrinology. Many pediatric departments (42.2%) experienced adult 21-OHD patients, and 115 patients (53 males, mean age of 26) in 46 institutions were identified. Whereas almost two-thirds of pediatric endocrinologists regarded the problems of counterparts and cooperation as hindrance of transition medicine, the major reason for continuing to be treated in pediatrics was the patient's own request. The prevalence of long-term complications including obesity, osteoporosis, infertility, menstrual disorder, gender dysphoria, and testicular adrenal rest tumor were 27.5%, 8.8%, 11.1%, 26.3%, 7.1%, 12.5%, respectively, which is comparable to those of other cohorts previously reported. However, several items, especially infertility and osteoporosis were not checked well enough in adult 21-OHD patients treated in pediatrics. Though 44 of 62 female patients had genital reconstructive surgery, more than half of them were not followed up by gynecologists or pediatric urologists. Quite a few adult 21-OHD patients had been followed up in pediatrics even after coming of age; however, surveillance by pediatric endocrinologists of gynecological, reproductive, and mental problems may be insufficient. Therefore, multidisciplinary approaches should be required in transition medicine for 21-OHD and prerequisite for graduation of pediatrics. Pediatric endocrinologists will need to play a leading role in the development of transition systems.

Central hypothyroidism improves with age in very young children with Prader-Willi syndrome.

OBJECTIVE: Abnormalities in the hypothalamic-pituitary-thyroid (HPT) axis have been implicated in Prader-Willi syndrome (PWS); however, limited information is currently available on age-dependent alterations in the HPT axis. We herein investigated age-dependent differences in thyroid hormone levels in PWS children. DESIGN/PATIENTS/MEASUREMENTS: Free T4 (FT4), free T3 (FT3) and thyroid-stimulating hormone (TSH) concentrations were retrospectively compared between genetically confirmed PWS children (N = 43, median age: 11.2 months) and controls (N = 85, median age: 14.5 months) matched for age, sex, body weight-SD score (SDS), height-SDS, body mass index-SDS and serum albumin level, a marker of the nutritional status. Subjects were subdivided into two groups based on their age: an infant group aged between 1 and 11 months (PWS: N = 22, controls: N = 30) and a toddler group aged between 12 and 47 months (PWS: N = 21, controls: N = 55). None of the subjects had ever been treated with growth hormone or levothyroxine. RESULTS: After adjustments for confounding variables, in the infant group, FT4 levels (pmol/L) were significantly lower in PWS (11.24 in PWS vs 14.32 in controls, P = .0002), whereas no significant differences were observed in FT3 or TSH levels. In the toddler group, no significant differences were noted in FT4 (12.23 in PWS vs 15.31 in controls, P = .10), FT3 or TSH levels. The FT3/FT4 ratio was significantly increased in PWS in both groups. FT4 levels were positively correlated with age in PWS. CONCLUSIONS: Infants with PWS had lower FT4 levels, but FT3 levels were normal, indicating that the levothyroxine replacement therapy may not need to be routinely performed.

A Multicenter Prospective Survey on Early-Onset Inflammatory Bowel Disease in Japan.

INTRODUCTION: The incidence of early-onset inflammatory bowel disease is increasing in Japan. OBJECTIVE: This study aimed to analyze the treatment and progress of early-onset inflammatory bowel disease. METHODS: This prospective survey evaluated the data of 43 patients aged <8 years who were diagnosed with inflammatory bowel disease (IBD) from the time of diagnosis to 36 months after registration. RESULTS: A total of 12 patients with Crohn's disease (CD), 21 with ulcerative colitis (UC), and 3 with unclassified IBD were enrolled. The mean disease onset age was 3 years and 7 months. Colon and anal lesions were present in 100 and 50% of patients with CD, respectively. Granulomas were detected in 5 patients (41.7%). Dietary elimination including elemental diet was performed in all patients. Eleven patients (91.7%) were in remission by initial induction therapy, and 72.7% maintained remission for 36 months. Three patients (14.3%) with UC had familial history, 71.4% had pancolitis-type UC, and 66.7% exhibited disease of moderate severity. Colectomy was performed in 4 patients (21.1%). Eighteen patients (85.7%) were in remission by initial induction therapy; however, only 15.8% maintained remission for 36 months. Anal complication was more prevalent in infantile-onset IBD than in childhood-onset IBD (p = 0.014). CONCLUSIONS: Among Japanese patients aged <8 years who were diagnosed with IBD, colitis-type disease was more common in CD and pancolitis was more common in UC. As the courses of several patients were severe, identifying primary immunodeficiency appears to be necessary to confirm background disease.

Renal function in short-statured children born small for gestational age and treated with growth hormone.

BACKGROUND: Children born small for gestational age (SGA), particularly when associated with an extremely low birthweight (ELBW), have a higher risk of renal dysfunction. Growth hormone (GH) treatment is used to treat short-statured children born SGA; however, its effects on renal function remain elusive, especially in those born SGA with ELBW. METHODS: Short-statured children born SGA (N = 42) were included. Subjects were subdivided into two groups based on their birthweight: the ELBW group (N = 15) with a birthweight of <1,000 g, and the non-ELBW group (N = 27) with birthweights ranging between 1,000 and 2,500 g. The creatinine-based estimated glomerular filtration rates (eGFR) before (pre-eGFR) and 5 years after GH treatment (post-eGFR) were compared. Correlations between eGFR, anthropometric, or birth parameters, and cumulative GH dose were evaluated using Spearman's rank correlation coefficient. RESULTS: The ELBW group had a lower pre- and post-eGFR than the non-ELBW group. Five-year GH treatment did not significantly reduce eGFR in either group. Post-eGFR was positively associated with gestational week and birthweight. However, the cumulative GH dose was not correlated with pre-eGFR, post-eGFR, or percentage change in eGFR (%ΔeGFR). The change in bodyweight standard deviation score during GH treatment was positively correlated with %ΔeGFR in the ELBW group. CONCLUSIONS: The current results indicated that GH treatment was unlikely a risk for the reduction in eGFR in short-statured children born SGA. However, eGFR should be carefully monitored, especially in those born SGA with ELBW because these subjects had lower eGFR than non-ELBW subjects.

Growth hormone treatment for extremely low birthweight children born small for gestational age.

BACKGROUND: The effectiveness of growth hormone (GH) treatment for height gain in short-stature children born small for gestational age (SGA) with extremely low birthweight (ELBW; birthweight <1,000 g) remains largely unknown. METHODS: In study 1, 35 prepubertal Japanese children born SGA with ELBW were categorized into three groups based on the presence or absence of catch-up growth by age 3 (CU(+) and CU(-), respectively) and GH treatment (GH(+) and GH(-), respectively). Height standard deviation (SD) scores (HT-SDS) in the CU-/GH+ group (n = 19) were compared with those in the age-matched CU+/GH- (n = 9) and CU-/GH- groups (n = 7). In study 2, 66 prepubertal Japanese SGA children treated with GH were divided into three groups by birthweight: <1,000 g (n = 19), 1,000-2,000 g (n = 20), and >2,000 g (n = 27). Changes in HT-SDS during the initial 3 years of GH treatment were compared among the three groups. RESULTS: In study 1, the mean HT-SDS in the CU-/GH+ group (-1.15 SD) was similar to that in the CU+/GH- group (-1.39 SD) but higher than that in the CU-/GH- group (-2.24 SD). In study 2, GH achieved a height gain of +1.62 SD in the ELBW group, which was similar to that in the other groups (1,000-2,000 g: +1.46 SD, >2,000 g: +1.53 SD). CONCLUSIONS: Growth hormone treatment in short-stature children born SGA with ELBW increased HT-SDS, which was similar to that in SGA children born with a birthweight ≥1,000 g. These results indicate that GH treatment may be an effective approach to promote adequate growth recovery for short-stature children born SGA with ELBW.

Visceral adipose tissue resides within the reference range in children with Prader-Willi syndrome receiving nutritional intervention on a regular basis.

Nutritional intervention for maintaining an appropriate body composition is central to the management of Prader-Willi syndrome (PWS). Despite evidence that visceral adipose tissue (VAT) is associated with increased metabolic risks, the effects of nutritional intervention on fat distribution have not been evaluated for PWS children. We herein investigated fat distribution in 20 genetically diagnosed PWS children (9 males and 11 females); 17 of which received nutritional intervention with or without growth hormone (GH) treatment [GH-treated group (n = 8), GH-untreated group (n = 9)]. GH treatment continued for median of 4.9 years. GH treatment significantly increased height standard deviation score (SDS) whereas body weight SDS and body mass index SDS were not affected in GH-treated group. In GH-untreated group, height SDS significantly decreased during approximately 5 years of follow-up. Fat distribution was evaluated at the median age of 6.93 years in GH-treated group and 7.01 years in GH-untreated group. VAT was maintained within the reference range in both groups. Subcutaneous adipose tissue (SAT) was elevated in GH-untreated groups compared to reference values whereas it was not in GH-treated group. The remaining three subjects, who had never received nutritional intervention or GH treatment, showed increased VAT and SAT. In conclusion, nutritional intervention is beneficial in maintaining VAT within the reference range during childhood, although excessive nutritional intervention may cause unfavorable effect on linear growth.

Fat distribution in short-stature children born small for gestational age.

BACKGROUND: Children born small for gestational age (SGA) with catch-up growth are at high risk for developing obesity; however, the characteristics of body composition, especially fat distribution, before and after growth hormone (GH) treatment in SGA children without catch-up growth remains largely unknown. METHODS: Anthropometric characteristics, body composition by dual-energy X-ray absorption, and fat distribution by computed tomography at the umbilical level were examined in 27 prepubertal short-stature children born SGA before and 1 year after GH treatment. RESULTS: Before GH treatment, short-stature SGA children had lean phenotypes, and both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were significantly lower than the age- and sex-matched Japanese reference values. Growth hormone treatment significantly increased height standard deviation scores (SDS), without affecting body mass index SDS. Percentage fat mass decreased with GH treatment; however, fat mass was not altered. Both VAT and SAT were significantly lower than the reference values after GH treatment. The ratio of VAT over SAT significantly increased by GH treatment. CONCLUSIONS: Both VAT and SAT were within or below the age- and sex-matched Japanese reference values in short-stature children born SGA before and after GH treatment, indicating that GH treatment may not have unfavorable effects on adiposity in short-stature children born SGA, although it may alter fat distribution.

The updated JSPGHAN guidelines for the management of Helicobacter pylori infection in childhood.

The Japan Pediatric Helicobacter pylori Study Group published the first guidelines on childhood H. pylori infection in 1997. They were later revised by the Japanese Society for Pediatric Gastroenterology, Hepatology and Nutrition (JSPGHAN). The H. pylori eradication rates, when employing triple therapy with amoxicillin and clarithromycin, currently recommended as the first-line therapy of H. pylori infection in Japan, have substantially decreased, creating an important clinical problem worldwide. In Japanese adults, the "test-and-treat" strategy for H. pylori infection is under consideration as an approach for gastric cancer prevention. However, the combined North American and European pediatric guidelines have rejected such a strategy for asymptomatic children. As risk for gastric cancer development is high in Japan, determining whether the "test-and-treat" strategy can be recommended in children has become an urgent matter. Accordingly, the JSPGHAN has produced a second revision of the H. pylori guidelines, which includes discussion about the issues mentioned above. They consist of 19 clinical questions and 34 statements. An H. pylori culture from gastric biopsies is recommended, not only as a diagnostic test for active infection but for antimicrobial susceptibility testing to optimize eradication therapy. Based upon antimicrobial susceptibility testing of H. pylori strains (especially involving clarithromycin), an eradication regimen including use of the antibiotics to which H. pylori is susceptible is recommended as the first-line therapy against H. pylori-associated diseases. The guidelines recommend against a "test-and-treat" strategy for H. pylori infection for asymptomatic children to protect against the development of gastric cancer because there has been no evidence supporting this strategy.

Policy statement of enteral nutrition for preterm and very low birthweight infants.

For preterm and very low birthweight infants, the mother's own milk is the best nutrition. Based on the latest information for mothers who give birth to preterm and very low birthweight infants, medical staff should encourage and assist mothers to pump or express and provide their own milk whenever possible. If the supply of maternal milk is insufficient even though they receive adequate support, or the mother's own milk cannot be given to her infant for any reason, donor human milk should be used. Donors who donate their breast milk need to meet the Guideline of the Japan Human Milk Bank Association. Donor human milk should be provided according to the medical needs of preterm and very low birthweight infants, regardless of their family's financial status. In the future, it will be necessary to create a system to supply an exclusive human milk-based diet (EHMD), consisting of human milk with the addition of a human milk-derived human milk fortifier, to preterm and very low birthweight infants.

Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea: A Nationwide Study in Japan.

OBJECTIVE: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). STUDY DESIGN: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. RESULTS: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. CONCLUSIONS: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia.

Genotype-phenotype correlation analysis in Japanese patients with Noonan syndrome.

Noonan syndrome (NS) is a heterogeneous disorder with multiple congenital malformations. Recent advances in molecular and genetic approaches have identified a number of responsible genes for NS, most of which are components of the RAS/MAPK signaling pathway, and genotype-phenotype correlation analyses have been extensively performed; however, analysis of Japanese NS patients is limited. Here, we evaluated clinical characteristics in genetically diagnosed NS patients and their relationships to genotypes. A total of 48 clinically diagnosed NS were included, and responsible mutations were identified in 39 patients (81.3%) with PTPN11 mutations being the most prevalent followed by SOS1 mutations. Cardiac anomalies including pulmonary stenosis and hypertrophic cardiomyopathy were most prevalent (87.2%), and the prevalence of hypertrophic cardiomyopathy was greater in patients without PTPN11 mutations than in those with PTPN11 mutations. Short stature was the second-most prevalent (69.2%) characteristic, and present height SD score was significantly associated with height SD score at 1 year old. Patients with SOS1 mutations had greater present height SD score and better growth during infancy. These findings suggest the presence of a genotype-phenotype correlation in Japanese patients with NS, which enables us to use genetic information to predict the clinical course and may allow for genotype-based medical interventions.

Oral esomeprazole in Japanese pediatric patients with gastric acid-related disease: Safety, efficacy, and pharmacokinetics.

BACKGROUND: Proton pump inhibitors (PPI) are widely used for the treatment of gastric acid-related disease, but they are not approved for use in children in Japan. To assess the safety, pharmacokinetics, pharmacodynamics, and efficacy (gastrointestinal symptom improvement) of PPI in Japanese pediatric patients with gastric acid-related disease, we conducted an 8 week, open-label, parallel-group, multicenter, phase I/III study of once-daily oral esomeprazole use. METHODS: Japanese children, aged 1-14 years with gastric acid-related disease, were stratified by weight and age into five groups (10 patients/group) to receive esomeprazole as granules for suspension (10 mg) or capsules (10 mg or 20 mg) once daily. RESULTS: Esomeprazole was absorbed and eliminated rapidly in all groups, with a median time to reach maximum plasma concentration of 1.47-1.75 h, an arithmetic mean terminal elimination half-life of 0.80-1.37 h, and a weight-correlated apparent total body clearance of 0.216-0.343 L/h/kg. Area under the plasma concentration-time curve during a dosage interval and maximum plasma drug concentration were generally higher in groups given a higher dose (20 mg) or with a lower age/weight, but also in patients identified as poor metabolizers on cytochrome P450 2C19 genotype. Most patients who had any upper gastrointestinal symptoms at baseline were asymptomatic at the end of the study. Thirty-three patients (66%) reported ≥1 adverse events, including three patients who reported serious adverse events not judged to be causally related to esomeprazole. CONCLUSIONS: Oral esomeprazole, at 10 mg or 20 mg once daily, had a similar safety, efficacy, and pharmacokinetic profile in Japanese pediatric patients to that previously seen in adults and Caucasian children.

Three patients with Schaaf-Yang syndrome exhibiting arthrogryposis and endocrinological abnormalities.

MAGEL2 is the paternally expressed gene within Prader-Willi syndrome critical region at 15q11.2. We encountered three individuals in whom truncating mutations of MAGEL2 were identified. Patients 1 and 2, siblings born to healthy, non-consanguineous Japanese parents, showed generalized hypotonia, lethargy, severe respiratory difficulty, poor feeding, and multiple anomalies including arthrogryposis soon after birth. We carried out whole-exome sequencing, which detected a MAGEL2 mutation (c.1912C>T, p.Gln638*, heterozygous). The patients' father was heterozygous for the mutation. Patient 3 was a female infant, showed respiratory difficulty reflecting pulmonary hypoplasia, generalized hypotonia, feeding difficulty and multiple anomalies soon after birth. Targeted next-generation sequencing detected a novel heterozygous mutation in MAGEL2 (c.3131C>A, p.Ser1044*). This mutation was not found in the parents. MAGEL2 mutations, first reported to be the cause of the Prader-Willi like syndrome with autism by Schaaf et al. (2013) Nature Genetics, 45: 1405-1408 show the wide range of phenotypic spectrum from lethal arthrogryposis multiplex congenital to autism spectrum disorder (ASD) and mild intellectual disability (ID). Our results indicate that MAGEL2 mutations cause multiple congenital anomalies and intellectual disability accompanied by arthrogryposis multiplex congenita and various endocrinologic abnormalities, supporting that the view that clinical phenotypes of MAGEL2 mutations are variable.

Vitamin B1 Deficiency Related to Excessive Soft Drink Consumption in Japan.

The aim of this study was to clarify the picture of vitamin B1 deficiency (VB1D) caused by excessive soft drink consumption in Japan. A nationwide survey of children with soft drink-induced VB1D was conducted using a structured research form. Patient information was obtained from 2 sources: training hospitals for board-certified pediatricians and those identified by a database search. We obtained data from 33 children. Twenty-one children had a nonnurturing home environment. The median duration of excessive soft drink intake was 3.5 months and the daily intake was 1000 mL or more in 25 children. Infection was the most common reason for excessive soft drink consumption. Only 4 children had the classical triad of Wernicke encephalopathy. One child died, and 12 had neurological sequelae. A majority of children with soft drink-induced VB1D did not have a nurturing home environment. It is imperative to establish measures to prevent future cases of VB1D.

Visceral adipose tissue increases shortly after the cessation of GH therapy in adults with Prader-Willi syndrome.

GH therapy in pediatric patients with Prader-Willi syndrome (PWS) improves body composition, but discontinuation of GH after achieving adult height has been implicated in its deterioration. Although there is evidence for the deleterious effects of visceral adipose tissue (VAT) rather than subcutaneous adipose tissue (SAT) on the development of obesity-related complications, the effects of GH discontinuation on fat distribution in adults with PWS has not been fully investigated. Therefore, we utilized dual-energy X-ray absorptiometry (DEXA) and abdominal computed tomography (CT) to compare the fat distribution between before and 6 months or 12 months after the cessation of GH therapy in 7 adult PWS patients. GH therapy was initiated at a mean age of 4.1 ± 1.4 years and discontinued at a mean age of 18.9 ± 1.8 years. Serum IGF-1 levels were decreased by discontinuation of GH therapy. Fat mass was significantly increased 6 and 12 months after GH cessation, whereas muscle mass and bone mineral density were unchanged during both study periods. Abdominal CT analysis revealed that elevations in fat mass were due to increases in VAT rather than SAT. Circulating low-density lipoprotein (LDL) cholesterol levels were significantly elevated 6 months after GH cessation. In conclusion, discontinuation of GH therapy caused rapid increases in visceral adipose tissue and LDL cholesterol levels. These findings indicate that continuation of GH therapy may be a therapeutic option to maintain body composition; however, further studies regarding the long-term benefits and adverse effects of GH therapy in adults with PWS are required.

Attitudes of pediatricians toward Children's consumption of ionic beverages.

BACKGROUND: The aim of our study was to clarify the attitudes of pediatricians toward children's consumption of ionic beverages. METHODS: A questionnaire survey of pediatric practitioners' attitudes toward the consumption of ionic beverages was administered to 537 doctors under 60 years of age who were members of the Japanese Pediatric Society. RESULTS: We received 215 valid responses from 182 board-certified pediatric specialists and 31 non-specialists. Approximately 60% of respondents recommended ionic beverages either often or sometimes. About half of all respondents cautioned patients about excessive consumption. About 40% had experienced at least one instance of excessive consumption characterized by acute symptoms including vomiting, diarrhea, and pyrexia. Specialists were more likely to recommend ionic beverages for oral rehydration than did non-specialists. Non-specialists more often recommended ionic beverages to patients with pyrexia. CONCLUSIONS: Pediatricians' attitudes toward children's consumption of ionic beverages were generally appropriate. Pediatric specialists' attitudes were more appropriate than were those of non-specialists.