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BACKGROUND: Molecular characterization in pediatric papillary thyroid cancer (PTC), distinct from adult PTC, is important for developing molecularly targeted therapies for progressive radioiodine-refractory ((131)I-refractory) PTC. METHODS: PTC samples from 106 pediatric patients (age range: 4.3–19.8 years; n = 84 girls, n = 22 boys) who were admitted to SNUH (January 1983–March 2020) were available for genomic profiling. Previous transcriptomic data from 125 adult PTC samples were used for comparison. RESULTS: We identified genetic drivers in 80 tumors: 31 with fusion oncogenes (RET in 21 patients, ALK in 6 patients, and NTRK1/3 in 4 patients); 47 with point mutations (BRAF(V600E) in 41 patients, TERT(C228T) in 2 patients [1 of whom had a coexisting BRAF(V600E)], and DICER1 variants in 5 patients); and 2 with amplifications. Fusion oncogene PTCs, which are predominantly detected in younger patients, were at a more advanced stage and showed more recurrent or persistent disease compared with BRAF(V600E) PTCs, which are detected mostly in adolescents. Pediatric fusion PTCs (in patients

Patients with craniopharyngioma are susceptible to autonomic dysfunction as a result of hypothalamic damage. We evaluated indices of heart rate variability (HRV) in patients with childhood-onset craniopharyngioma to investigate autonomic function and its relationship with components of the metabolic syndrome (MetS). This cross-sectional, case-only study included 53 patients (10–30 years of age). We measured the standard deviation of all normal R-R intervals (SDNN) and total power indicating overall HRV, the root-mean square of the difference of successive R-R intervals (RMSSD) and high frequency indicating parasympathetic modulation, and low frequency. These indices were compared according to the presence of the MetS. During the mean 10.8 years of follow-up, 25% of patients were diagnosed with the MetS. Patients with the MetS showed significantly lower levels of SDNN (29.0 vs. 40.6 ms), total power (416.1 vs. 1129.6 ms2), RMSSD (20.1 vs. 34.5 ms), high frequency (94.7 vs. 338.5 ms2), and low frequency (94.5 vs. 289.4 ms2) than those without (p

Background: Discontinuing growth hormone (GH) treatment during the transition to adulthood has been associated with adverse health outcomes in patients with childhood-onset growth hormone deficiency (CO-GHD). This study investigated the metabolic changes associated with interrupting GH treatment in adolescents with CO-GHD during the transition period.Methods: This study included 187 patients with CO-GHD who were confirmed to have adult GHD and were treated at six academic centers in Korea. Data on clinical parameters, including anthropometric measurements, metabolic profiles, and bone mineral density (BMD) at the end of childhood GH treatment, were collected at the time of re-evaluation for GHD and 1 year after treatment resumption.Results: Most patients (n=182, 97.3%) had organic GHD. The median age at treatment discontinuation and re-evaluation was 15.6 and 18.7 years, respectively. The median duration of treatment interruption was 2.8 years. During treatment discontinuation, body mass index Z-scores and total cholesterol, low-density lipoprotein, and non-high-density lipoprotein (HDL) cholesterol levels increased, whereas fasting glucose levels decreased. One year after GH treatment resumption, fasting glucose levels, HDL cholesterol levels, and femoral neck BMD increased significantly. Longer GH interruption (>2 years, 60.4%) resulted in worse lipid profiles at re-evaluation. The duration of interruption was positively correlated with fasting glucose and non-HDL cholesterol levels after adjusting for covariates.Conclusion: GH treatment interruption during the transition period resulted in worse metabolic parameters, and a longer interruption period was correlated with poorer outcomes. GH treatment should be resumed early in patients with CO-GHD during the transition period.

Background: Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study.Methods: CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400).Results: The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0).Conclusion: Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

There is a lack of studies regarding the long-term outcomes of Asian adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. We hypothesized that adults with CAH are at higher metabolic risk than their age-, and sex-matched controls. We further investigated the long-term health outcome-related factors in adults with CAH. We compared metabolic risk between adults with CAH (71 men, 93 women) and age-, and sex-matched controls (190 men, 261 women) from the Korean National Health and Nutrition Examination Survey data. The presence of obesity, testicular adrenal rest tumors (TARTs), and menstrual irregularity was assessed. Hormone status and treatment regimens were compared according to the presence of adverse outcomes. The median age was 27.0 y and 28.0 y for men and women, respectively. Adults with CAH had a higher waist circumference (88.0 vs. 82.3 cm in men, and 83.5 vs. 72.3 cm in women), and blood pressure (125.0 vs. 113.0 mmHg in men, and 120.0 vs. 104.0 mmHg in women) than age- and sex-matched controls (PPP

Low-iodine diet (LID) is a crucial preparation for radioactive iodine (RAI) treatment or scan in thyroid cancer. The aim of this study is to analyze the influence of thyroid stimulating hormone (TSH) stimulation protocols and other clinical factors on LID adequacy. Thyroid cancer patients who underwent LID for RAI scan or treatment were retrospectively analyzed. Patients were guided to have LID for 2 weeks before RAI administration and urine iodine/creatinine ratio (UICR, μg/g Cr) was measured. TSH stimulation was conducted using either thyroid hormone withdrawal (THW) or recombinant human TSH (rhTSH) injection. Adequacy of LID was classified by UICR as ‘excellent (< 50)’, ‘adequate (50–100)’, ‘inadequate (101–250)’ and ‘poor (> 250)’. A total of 1715 UICR measurements from 1054 patients were analyzed. UICR was significantly higher in case of rhTSH use than THW (72.4 ± 48.1 vs. 29.9 ± 45.8 μg/g Cr, P < 0.001). In patients who underwent LID twice using both TSH stimulation protocols alternately, UICR was higher in case of rhTSH than THW regardless of the order of method. Among clinical factors, female, old-age, and the first LID were significant factors to show higher UICR. Although the adequacy of LID was ‘adequate’ or ‘excellent’ in most patients, multivariate analysis demonstrated that THW method, male, young age, and prior LID-experience were significant determinants for achieving ‘excellent’ adequacy of LID. In conclusion, UICR was higher and the proportion of ‘excellent’ LID adequacy was lower with rhTSH than with THW. UICR was higher also in women, old-age, and LID-naïve patients. Further researches are required to suggest effective methods to reduce body iodine pool in case of rhTSH use and to validate the efficacy of such methods on outcomes of RAI treatment.

Background The short-stature homeobox-containing gene (SHOX) is one of the major growth genes in humans. The clinical spectrum of SHOX haploinsufficiency ranges from Leri–Weill dyschondrosteosis to idiopathic short stature. Herein, we describe the clinical and genetic characteristics of 23 Korean patients with SHOX deficiency disorders. Methods Medical records of 23 patients (19 females and 4 males) from 15 unrelated families who were genetically confirmed to have SHOX deficiency were retrospectively reviewed. SHOX gene deletions or mutations were determined by sequence analyses using multiplex ligation-dependent probe amplification, chromosomal microarray, and/or Sanger sequencing methods. Results In the 15 families, 9 probands were de novo cases. All 23 patients showed mesomelia. Madelung deformity and tibia vara were observed in 13 (56.5%) and 3 (13.1%) patients, respectively. Genetically, 11 (73.3%) of the 15 families showed SHOX deletions of various sizes, and the other 4 families harboured SHOX sequence variants. Four patients had undergone orthopaedic surgeries (3 for tibia vara and 1 for Madelung deformity). Among 7 patients who had received growth hormone treatment for ≥1 year, 5 showed good responses, with a median first-year change-in-height standard deviation score of +0.6. There were no significant differences in the clinical characteristics of the deletion and point mutation groups. Conclusions A high index of suspicion and the genetic confirmation of SHOX deficiency are helpful for the timely management of the condition and are needed to provide genetic counselling to the family members of the patients.

Background Silver-Russell syndrome (SRS) is a pre- or post-natal growth retardation disorder caused by (epi)genetic alterations. We evaluated the molecular basis and clinical value of sequential epigenetic analysis in pediatric patients with SRS. Methods Twenty-eight patients who met≥3 Netchine-Harbison clinical scoring system (NH-CSS) criteria for SRS were enrolled;26 (92.9%) were born small for gestational age, and 25 (89.3%) showed postnatal growth failure. Relative macrocephaly, body asymmetry, and feeding difficulty were noted in 18 (64.3%), 13 (46.4%), and 9 (32.1%) patients, respectively. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) on chromosome 11p15 was performed as the first diagnostic step. Subsequently, bisulfite pyrosequencing (BP) for imprinting center 1 and 2 (IC1 and IC2) at chromosome 11p15, MEST on chromosome 7q32.2, and MEG3 on chromosome 14q32.2 was performed. Results . Seventeen (60.7%) patients exhibited methylation defects, including loss of IC1 methylation (N=14; 11 detected by MS-MLPA and three detected by BP) and maternal uniparental disomy 7 (N=3). The diagnostic yield was comparable between patients who met three or four of the NH-CSS criteria (53.8% vs 50.0%). Patients with methylation defects responded better to growth hormone treatment. Conclusions NH-CSS is a powerful tool for SRS screening. However, in practice, genetic analysis should be considered even in patients with a low NH-CSS score. BP analysis detected additional methylation defects that were missed by MS-MLPA and might be considered as a first-line diagnostic tool for SRS.

Objective Pheochromocytoma and paraganglioma (extra-adrenal pheochromocytoma) are rare neuroendocrine tumors that arise from the neuroendocrine cells. Chronic hypoxia is known as a possible cause, and a strong link between cyanotic congenital heart disease and these tumors has been reported. However, reports of phechromocytoma/paraganglioma in Fontan patients were scarce. We herein report seven cases of phechromocytoma/paraganglioma after Fontan operation at a single tertiary center. Methods We retrospectively reviewed medical records and imaging studies who diagnosed as phechromocytoma/paraganglioma after Fontan operation in Seoul National University Children's Hospital. Results Seven patients were identified during follow-up after Fontan operation, and the prevalence was 2.5% among Fontan patients greater than 10 years old on active follow-up. Three patients were diagnosed as phechromocytoma and 4 patients as paraganglioma. Median time interval between Fontan operation and diagnosis of pheochromocytoma/paraganglioma was 21.4 years (range, 10.4-29.7 years). Resting percutaneous oxygen saturation varied from 77% to 94%. All patients underwent complete tumor resection. Phechromocytoma recurred in two patients, of whom one patient died at the age of 18 years due to the tumor progression with multiple metastasis and aggravation of heart failure with profound cyanosis. Pheochromocytoma/paraganglioma developed after hepatocellular carcinoma in two patients. Conclusion Phechromocytoma/paraganglioma could occur in Fontan patients more than expected. Because it is curable by tumor resection during its early phase, early diagnosis and treatment of pheochromocytoma are crucial in Fontan patients not to make hemodynamic deterioration and aggravation of heart failure.

Bisphenol A (BPA) has been reported to be associated with adverse health effects, including high blood pressure (BP). BPA is also suspected to cross placenta in pregnancy and might affect children’s health. The present study was aimed to evaluate the effect of prenatal exposure to BPA on the BP of the child at the age of 4. We followed up 645 children at the age of 4 who were born from women who participated midterm during their pregnancy in a birth cohort study from August 2008 to July 2011. Because BPA and BP showed nonlinear association, we constructed a piecewise regression model to examine the association between urinary BPA concentration of mother at around 20 weeks of gestation and BP of the child at age 4 and to determine threshold level of BPA for the association. Diastolic BP of the children was positively associated with maternal urinary concentration of BPA above the threshold level measured at around 20 weeks of gestation. For 1 log unit increment of prenatal urinary BPA concentration, diastolic BP was increased by 7.9 mm Hg (SE=2.072; P =0.0001) after adjusting potential confounders. Pulse pressure was decreased by −8.0 mm Hg (SE=2.528; P =0.0015). However, systolic BP was not significantly associated with prenatal BPA concentration. The present study suggests that exposure to BPA during pregnancy is associated with higher diastolic BP of the children above a certain threshold (4.5 μg/g creatinine).

OBJECTIVE Patients with Turner syndrome (TS) are at high risk for cardiovascular morbidity and mortality due to aortic dilation. We evaluated the prevalence of hypertension and its risk factors and investigated the relationship between systolic hypertension and aortic diameter in young patients with TS. DESIGN Observational, cross-sectional study. PATIENTS AND MEASUREMENTS Forty-two patients with TS (15-35 years) who had achieved final adult heights underwent 24-h ambulatory blood pressure monitoring (ABPM). Fasting glucose, insulin and lipid profiles were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Echocardiography was performed to evaluate aortic diameters (aortic annulus, aortic root at the sinuses of Valsalva, sinotubular junction and ascending aorta), which were converted into Turner-specific z-scores. RESULTS Systolic and/or diastolic hypertension was identified in 71.4% (n = 30) of patients, as assessed by 24-hour ABPM. Twenty-eight patients (66.7%) were nondippers. Patients with systolic hypertension (n = 8, 19.0%) had a higher weight, waist circumference and HOMA-IR levels than those without hypertension (P

Background Autonomic nervous system dysfunction is implicated in the development of hypothalamic obesity. We investigated the relationship between hypothalamic involvement (HI), central obesity, and cardiac autonomic dysfunction by assessing heart rate variability (HRV) indices in patients with childhood-onset craniopharyngioma. Methods A cross-sectional study of 48 patients (28 males, 10–30 years old) with hypothalamic damage after childhood-onset craniopharyngioma was performed. Postoperative HI was graded as mild (n = 19) or extensive (n = 29) on magnetic resonance imaging. Anthropometry, body composition and HRV indices including the standard deviation of all normal R-R intervals (SDNN) and total power (TP) as overall variability markers, root-mean square differences of successive R-R intervals (RMSSD) and high frequency (HF) as parasympathetic modulation markers, and low frequency (LF) as a sympathetic/sympathovagal modulation marker were measured. Results Patients with extensive HI had increased means of body mass index, waist circumference, and fat mass than those with mild HI (P < 0.05, for all). Centrally obese patients had a lower mean HF, a parasympathetic modulation marker, than centrally non-obese patients (P < 0.05). The extensive HI group had lower means of overall variability (SDNN and TP), parasympathetic modulation (HF), and sympathetic/sympathovagal modulation (LF) than the mild HI group (P < 0.05, for all). The interaction effect of HI and central obesity on HRV indices was not significant. In models adjusted for age, sex, and family history of cardiometabolic disease, the means of the overall variability indices (P < 0.05 for both SDNN and TP) and a sympathetic/sympathovagal modulation index (P < 0.05 for LF) were lower with extensive HI, without differences according to central obesity. Conclusions The reduced HRV indices with extensive HI suggests that hypothalamic damage may contribute to cardiac autonomic dysfunction, underscoring the importance of minimizing hypothalamic damage in patients with childhood-onset craniopharyngioma.

We established the timing of peak bone mass acquisition and body composition maturation and provide an age- and sex-specific body composition and bone density reference database using dual-energy X-ray absorptiometry in Korean subjects 10–25 years of age. Reference percentiles and curves were developed for bone mineral content (BMC), bone mineral density (BMD) of the whole body, the lumbar spine, and the femoral neck, and for fat mass (FM) and lean mass (LM) of 1969 healthy participants (982 males) who participated in the 2009–2010 Korean National Health and Nutrition Examination Survey. Additionally, bone mineral apparent density (BMAD), FM index, and LM index were calculated to adjust for body size. BMC and BMD at all skeletal sites as well as LM increased with age, reaching plateaus at 17–20 years of age in females and 20–23 years of age in males. The femoral neck was the first to reach a bone mass plateau, followed by the lumbar spine and then the whole body. Spine BMAD increased with age in both sexes, but femoral and whole-body BMAD remained the same over time. Females displayed a dramatic increase in FM during puberty, but the FM of males decreased until mid-puberty. These findings indicate that bone health and body composition should be monitored using a normal reference database until the late second to early third decade of life, when statural growth and somatic maturation are completed.

Context:Large-sample studies with long-term follow-up data are limited for pediatric patients with thyroid cancer.Objective:Secular changes in clinicopathological characteristics and outcomes in pediatric patients with thyroid cancer were investigated and compared with those of adults.Design and Patients:A retrospective review of 150 pediatric patients with thyroid cancer managed between 1980 and 2013 was conducted. The long-term outcomes of 124 patients followed up for 12 months or longer were evaluated. Predictors of recurrence-free survival (RFS) in pediatric patients with papillary thyroid cancer (ped-PTC group) were compared with those of 3071 adult patients.Results:The proportion of small tumors (Conclusions:The pathological characteristics and recurrence rates of pediatric thyroid cancer have not changed over 33 years. Although younger patients present with more advanced disease, multifocality rather than age at diagnosis predicted recurrence. Recurrence was higher in pediatric than adult patients with multifocal papillary thyroid cancer.

The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10–19 years old) and young adults (20–29 years old). Data from the Korea Health and Nutrition Examination Survey (2011–2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10–29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P P

Background Glycosylated hemoglobin (HbA1c) has been recommended as a diagnostic test for prediabetes and diabetes. Here, we evaluated the level of agreement between diagnoses based on fasting plasma glucose (FPG) versus HbA1c levels and determined optimal HbA1c cutoff values for these diseases in youth and young adults. Methods The study included 7,332 subjects (n=4,129, aged 10 to 19 years in youth group; and n=3,203 aged 20 to 29 years in young adult group) from the 2011 to 2016 Korea National Health and Nutrition Examination Survey. Prediabetes and diabetes were defined as 100 to 125 mg/dL (impaired fasting glucose [IFG]) and ≥126 mg/dL for FPG (diabetes mellitus [DM] by FPG [DMFPG]), and 5.7% to 6.4% and ≥6.5% for HbA1c, respectively. Results In the youth group, 32.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 72.2% with DMFPG had an HbA1c ≥6.5%. In the young adult group, 27.5% with IFG had an HbA1c level of 5.7% to 6.4%, and 66.6% with DMFPG had an HbA1c ≥6.5%. Kappa coefficients for agreement between the FPG and HbA1c results were 0.12 for the youth group and 0.19 for the young adult group. In receiver operating characteristic curve analysis, the optimal HbA1c cutoff for IFG and DMFPG were 5.6% and 5.9% in youths and 5.5% and 5.8% in young adults, respectively. Conclusion Usefulness of HbA1c for diagnosis of IFG and DMFPG in Koreans aged

PURPOSE The purpose of this study was to compare and contrast biopsychosocial characteristics and processes of change (POC) between 1-month quitters and relapsers among male smokers in Korea. METHODS This study employed a prospective study design. Forty-one male smokers were recruited on one university campus. The instruments used in this study included blood pressure (BP), body mass index, salivary cortisol, perceived stress, self-efficacy, and POC. After collection of baseline data, participants were encouraged to adopt smoking cessation, either by obtaining smoking cessation counseling or self-abstinence. Baseline data and data collected after 1 month from smoking cessation were compared. RESULTS The mean age of the participants was 24.9 years (SD = 1.90 years), and 51.2% were overweight or obese. According to results of the study, SBP, DBP, and perceived stress were significantly lower, whereas self-efficacy was significantly higher among quitters, compared with relapsers, after 1 month (p < .05). Results of within-group comparison indicated that, among POC, self-liberation, helping relationship, and reinforcement management showed a significant decrease among 1-month relapsers (p < .05), whereas, counter conditioning showed a significant increase among 1-month quitters (p < .05). CONCLUSIONS According to the results of this study, BP and perceived stress showed a significant decrease among 1-month quitters, whereas those less likely to utilize behavioral processes were more likely to have relapsed after 1 month.

The present experiment investigated the effects of skin pressure by foundation garments (girdle and brassiere) on the circadian rhythms of core temperature and salivary melatonin. Ten healthy females (18-23 years) maintained regular sleep-wake cycles for a week prior to participation in the experiment. The experiments were performed from June to August 1999 using a bioclimatic chamber controlled at 26.5 degrees C +/- 0.2 degrees C and 62% +/- 3% RH. Ambient light intensity was controlled at 500 lux from 07:30 to 17:30, 100 lux from 17:30 to 19:30, 20 lux from 19:30 to 23:30; there was total darkness from 23:30 to 07:30. The experiment lasted for 58h over three nights. The participants arose at 07:30 on the first full day and retired at 23:30, adhering to a set schedule for 24h, but without wearing foundation garments. For the final 24h of the second full day, the subjects wore foundation garments. Rectal and leg skin temperatures were measured continuously throughout the experiment. Saliva and urine were collected every 4h for the analysis of melatonin and catecholamines, respectively. Skin pressure applied by the foundation garments was in the range 11-17 gf/cm2 at the regions of the abdomen, hip, chest, and back. The main results were as follows: (1) Rectal temperatures were significantly higher throughout the day and night when wearing foundation garments. (2) The nocturnal level of salivary melatonin measured at 03:30 was 115.2 +/- 40.4 pg/mL (mean +/- SEM, N = 10) without and 51.3 +/- 18.4 pg/mL (mean +/- SEM, N = 10) with foundation garments. (3) Mean urinary noradrenaline excretion was significantly lower throughout the day and night when wearing foundation garments (p.05), but mean urinary adrenaline excretion was not different. The results suggest that skin pressure by clothing could markedly suppress the nocturnal elevation of salivary melatonin, resulting in an increase of rectal temperature.

Intracranial germ cell tumors (GCTs) frequently take an insidious clinical course before diagnosis. To date, clinical latency has been discussed in the context of germinoma in the suprasellar area and basal ganglia.In this study, we classified the clinical latency of intracranial GCTs into three categories and described their characteristics in order to understand the full spectrum of the phenomenon.In a cohort of 181 patients with intracranial GCTs, 17 patients had a delayed diagnosis of more than 3 months (90 days) from the initial brain magnetic resonance imaging to the definitive GCT diagnosis. Clinical records and radiological data of the patients were reviewed.The patients with a delayed diagnosis were categorized into three groups according to their tumor location: suprasellar (nine patients), basal ganglia (six patients), and pineal (two patients). Initial symptomatology corresponded with the tumor location: central diabetes insipidus for the suprasellar group, hemiparesis for the basal ganglia group, and precocious puberty for the pineal group. The overall survival of patients with germinoma and delayed diagnosis was significantly shorter than that of patients who were diagnosed within 3 months (P = 0.002).Clinical latency and delayed diagnosis are not restricted to germinomas in the suprasellar area and basal ganglia; they are canonical features of intracranial GCTs including pineal non-germinomatous GCTs. Early detection and proactive diagnosis of these tumors are required because diagnosis delay may negatively influence patient survival.

We measured bone mineral densities in 28 intracranial germ cell tumor long-term survivors. There was the high prevalence of osteoporosis and osteopenia, 25.0% and 42.9%, respectively, and three additional risk factors, male sex, a low lean mass, and adult growth hormone replacement, were identified.Intracranial germ cell tumor long-term survivors (iGCTLS) have many risk factors for osteoporosis, including irradiation from cancer therapy and multiple hormone deficiencies. However, no study of bone mineral density (BMD) has been conducted in iGCTLS because these tumors are rare. The aims of this study were to evaluate the prevalence of osteoporosis and to identify risk factors associated with reduced bone mass in iGCTLS.We evaluated BMD and body composition of 28 iGCTLS (10.9 ± 5.2 years after cancer treatment; 13 males) using dual-energy X-ray absorptiometry. To determine risk factors, we analyzed the medical history, including the nature of the tumor, treatment modality, endocrine status, hormone replacement therapy, lifestyle, and biochemical parameters.Twenty-five percent of iGCTLS were diagnosed with osteoporosis and 42.9% with osteopenia. Most males (92.3%) had low BMD. Lean mass (LM) was positively correlated with BMD in all regions of interest, and the starting age of adult growth hormone (GH) replacement was negatively correlated with the BMD Z-score at the femur neck. In logistic regression analysis, male sex and low LM were related to low BMD.The iGCTLS had a high prevalence of low BMD. We found that male sex, low LM, and delayed start of adult GH replacement were risk factors for osteoporosis. Therefore, the BMD of all iGCTLS should be evaluated, and if it is low, proper management should be started early.

Development of a testicular adrenal rest tumor (TART) is common in males with congenital adrenal hyperplasia, and it can be an important cause of infertility. In the present study, we observed the prevalence of TARTs, and analyzed its associated factors in patients with 21-hydroxylase deficiency. Testicular ultrasonography was performed in 48 postpubertal male patients aged 10.6 to 27.1 years. To determine whether patients were undertreated, we analyzed the serum 17-hydroxyprogesterone (17-OHP) levels to the time of ultrasonographic measurement and calculated the percentage of measurements when serum 17-OHP level was10 ng/mL relative to the total number of measurements during the follow-up period. We divided the 6-year period before ultrasonographic measurement (time 0) into three 2-year intervals and calculated the average concentration of serum 17-OHP in each interval to give a -2(nd) to 0 year-average concentration (-2-0YAC), -4-2YAC and -6-4YAC. A TART was detected by ultrasonography in 31 of 48 patients (64.6%) and the median maximal cross-sectional area of the TARTs was 0.71 (0.03, 4.95) cm(2). The corrected final adult height was lower, and -4-2YAC and body mass index were higher in patients with TART than in those without. After controlling for the type of 21-hydroxylase deficiency, hydrocortisone-equivalent dose, age, and -6-4YAC, the size of TART was associated with a high undertreatment percentage with a marginal statistical significance. These results suggest that strict disease control is mandatory and regular examination with testicular ultrasonography is recommended in male patients, regardless of the type of 21-hydroxylase deficiency.

Background There is ethnic variation in the variable number of tandem repeats of the insulin gene (INS VNTR), one of the susceptibility loci for developing type 1 diabetes (T1D). We evaluated the influence of the genotypes and subdivisions of INS VNTR on the development of T1D in Korean subjects. Methods The study included 352 Korean patients, under the age of 18 years who were diagnosed as having T1D, and 356 control subjects. The insulin − 23HphI A/T single nucleotide polymorphism was used as a marker of class I and III alleles. Surrounding polymorphisms at nucleotide positions + 1127, + 1140, + 2331 and + 2336 were determined as subdivisions of INS VNTR. Results Classes I/I, I/III and III/III were observed at frequencies of 95.8, 4.2 and 0% among all subjects, respectively. Class I/III genotype was significantly less frequent in patients with T1D than in controls (2.56 versus 5.90%; odds ratio 0.419; P = 0.039). In a subdivision analysis, the ID/ID genotype was decreased among patients (P = 0.017, adjusted P = 0.085) and the IC allele tended to increase. The frequency of the class I/III genotype was significantly lower among patients who were diagnosed when younger than 7 years of age than in controls (odds ratio 0.115; P = 0.011). Conclusions INS VNTR has predominance of class I over class III alleles and is associated with susceptibility to T1D in Koreans. In addition, INS VNTR shows distinctive susceptibility according to the age at the onset of T1D. Copyright © 2010 John Wiley & Sons, Ltd.

Objective We investigated whether the frequency, phenotype, and suppressive function of CD4+FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls. Design and Methods Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4–35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (–) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+CD25bright were co-cultured with autologous CD4+CD25− target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function. Results Despite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+CD25− T cells was significantly impaired in the TS (–) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (–) and TS (+) groups had lower frequencies of naive cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group. Conclusions The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.

On the basis of our previous findings that bright-light exposure during the daytime has profound influence on physiological parameters such as melatonin secretion and tympanic temperature in humans, we proposed the hypothesis that bright vs. dim light-exposure during the daytime has a different influence on the activity of the digestive system via the endocrine and/or autonomic nervous system. To examine this hypothesis, we conducted a series of counterbalanced experiments in which subjects stayed the daytime (7:00 to 15:00h) under either a dim (80 lux) or bright (5,000 lux) light condition. We measured gastrointestinal activity using a breath hydrogen (indicative of carbohydrate malabsorption) and an electrogastrography (EGG, indicative of gastric myoelectric activity) test. The results showed the postprandial breath hydrogen excretion during the following nighttime period after daytime exposure to the dim-light condition was significantly higher than under the bright-light condition (p < 0.05). In addition, the spectrum total power of the EGG recorded after taking the evening meal was significantly lower for the dim than bright-light condition (p < 0.05). These results support our hypothesis and indicate that dim-light exposure during the daytime suppresses the digestion of the evening meal, resulting in malabsorption of dietary carbohydrates in it.

The present experiment investigated the effects of skin pressure produced by a body compensatory brassiere on defecation activity. Seven healthy females (11-41 yrs) volunteered as participants, being free of medication and constipation. The experiment lasted 3 weeks. The participants did not wear the body compensatory brassiere for the first week, wore it during waking hours for the second week, and again did not wear it for the third week. Whenever they desired to defecate, they did so and then weighted the amount of feces immediately by themselves. Eating times, daily amounts of foods and drinks, their menu, work intensity and its duration, retiring and rising time were controlled to be as similar as possible from day to day. The main finding was that the amount of feces was significantly smaller during the second week (wearing the body compensatory brassiere) than the first and third weeks (not wearing the body compensatory brassiere). These observations are discussed in terms of the suppression of the parasympathetic nervous system and intestine motility, and the delayed transit time in the large intestine.