Autonomic Dysfunction is Associated with Increased Cardiometabolic Risk in Patients with Childhood-Onset Craniopharyngioma.

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 <0.05, for all). Individual components of the MetS including insulin resistance, serum triglycerides levels, and systolic blood pressure were inversely associated with SDNN, total power, RMSSD and high frequency. Higher overall variability and parasympathetic modulation were related to decreased odds ratios for having the MetS (OR 0.91, p=0.029 for SDNN; OR 0.91, p=0.032 for total power). In conclusion, autonomic dysfunction, as evidenced by reduced HRV indices, is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma.

Relationship between systolic hypertension assessed by 24-hour ambulatory blood pressure monitoring and aortic diameters in young women with Turner syndrome.

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 < 0.05 for all). After adjusting for covariates, HOMA-IR was independently associated with systolic hypertension (odds ratio 10.1, P = 0.043). After adjusting for age and bicuspid aortic valve, systolic hypertension was independently related to increased aortic diameter at the aortic annulus (ß = 1.064, P = 0.009) and sinotubular junction (ß = 1.124, P = 0.016). CONCLUSIONS: Hypertension is highly prevalent and independently associated with IR in young patients with TS. The significant relationship between systolic hypertension and aortic diameters underscores the importance of BP and IR control.

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls.

The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled. The levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and free testosterone (FT) were checked. The methylation-weighted (MW) average CAG repeat lengths were analyzed. The median ages at pubarche were 7.4 and 8.9 years in the PP and NP groups, respectively, and the levels of 17-OHP, DHEAS, and FT were similar in both groups. The PP group exhibited a higher DHEAS:DHEA ratio than the NP group (P=0.014). The medians of the MW average CAG repeat length of the AR gene were 22.4 for all subjects and did not differ among the PP (22.3), NP (22.4), and NC (22.2) groups. The AR CAG repeat lengths in the PP and NP groups did not correlate with DHEAS or FT levels. These results suggest that the AR CAG repeat length was not involved in the development of PP in Korean girls. However, excessive adrenal androgen levels, particularly those caused by increased sulfotransferase activity, might be important in the pathogenesis of PP.

Prevalence and Clinical Characteristics of Metabolically Healthy Obesity in Korean Children and Adolescents: Data from the Korea National Health and Nutrition Examination Survey.

Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) are differentiated by the presence of cardiometabolic risk factors (CMRFs) and insulin resistance (IR). This study aimed to evaluate the prevalence and clinical characteristics of MHO in Korean children and adolescents and to investigate the anthropometric, laboratory, and lifestyle predictors of MHO. This study included data from 530 obese subjects, aged 10-19 years, obtained from the Fourth Korea National Health and Nutrition Examination Survey. Subjects were classified into MHO and MUO groups according to the presence of CMRF (MHO(CMRF)/MUO(CMRF)) and degree of IR (MHO(IR)/MUO(IR)). Demographic, anthropometric, cardiometabolic, and lifestyle factors were compared between the groups. Logistic regression analysis and receiver operating characteristic curve analysis were performed to identify factors that predicted MHO. The prevalence of MHO(CMRF) and MHO(IR) in obese Korean youth was 36.8% (n = 197) and 68.8% (n = 356), respectively. CMRF profiles were significantly less favorable in MUO children. Longer and more vigorous physical activity and less protein intake were associated with MHO(CMRF) phenotype. The best predictors of MHO(CMRF) and MHO(IR) were waist circumference (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.77-0.88; P < 0.001) and body mass index (BMI) standard deviation score (OR, 0.24; 95% CI, 0.15-0.39; P < 0.001), respectively. The prevalence of MHO differed depending on how it was defined. To adequately manage obesity in youth, the approach to individuals with MHO and MUO should be personalized due to variation in clinical characteristics. Longitudinal studies are needed to evaluate long-term consequences of MHO.

Unfavorable Course of Subclinical Hypothyroidism in Children with Hashimoto's Thyroiditis Compared to Those with Isolated Non-Autoimmune Hyperthyrotropinemia.

Subclinical hypothyroidism (SCH) is a common problem in pediatric population, and the natural history of SCH varies depending on its etiology. Whether Hashimoto's thyroiditis (HT) negatively affects the natural course of SCH was investigated in pediatric patients without concomitant diseases. Predictors for levothyroxine medication were also evaluated. Medical records of 109 children with SCH (91 girls, 5?18 years) diagnosed between 2005 and 2014 were retrospectively reviewed. Patients were classified into HT (n = 37) and isolated non-autoimmune hyperthyrotropinemia (iso-NAHT, n = 72). During median 2 years of follow-up, only 10.1% of SCH patients eventually initiated levothyroxine, and HT patients showed a higher probability of requiring levothyroxine medication than iso-NAHT patients (21.6% vs. 4.2%). Underlying HT independently predicted deterioration of thyroid function, leading to levothyroxine medication (hazard ratios [HRs], 4.6 vs. iso-NAHT, P = 0.025). High titers of anti-thyroglobulin antibodies (TGAbs) predicted later medication in the HT group (HRs, 28.2 vs. normal TGAbs, P = 0.013). Most pediatric SCH showed benign and self-remitting courses. Underlying HT significantly increases the risk for levothyroxine medication, especially with high titers of TGAbs.

The Role of Overweight and Obesity on Bone Health in Korean Adolescents with a Focus on Lean and Fat Mass.

As the associations between pediatric overweight/obesity and bone health remain controversial, we investigated the effects of overweight/obesity as well as lean mass (LM) and fat mass (FM) on bone parameters in adolescents. Bone parameters were evaluated using dual-energy X-ray absorptiometry (DXA) data of 982 adolescents (aged 12-19 years) from the Korea National Health and Nutrition Examination Survey (2009-2010). Z-scores for LM, FM, bone mass, bone mineral density (BMD), and bone mineral apparent density (BMAD) using Korean pediatric reference values were used for analysis. Adolescents with overweight/obesity had significantly higher bone mass and density of the total-body-less-head (TBLH), lumbar spine, and femur neck than underweight or normal-weight adolescents (P < 0.001) after adjusting for vitamin D deficiency, calcium intake, and insulin resistance in both sexes. LM was positively associated with bone parameters at all skeletal sites in both sexes (P < 0.001). FM was negatively related to TBLH BMD in boys (P = 0.018) but was positively associated to BMD and BMAD of the lumbar spine and femur neck in girls. In conclusion, overweight/obesity and LM play a positive role in bone health in adolescents. The effect of FM on bone parameters is sex- and site-specific.

Factors Associated with the Presence and Severity of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Korean Children and Adolescents.

The aim of this study was to identify the risk factors for presence and severity of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in Korean children and adolescents. A retrospective chart review of children and adolescents newly diagnosed with T1DM was conducted in seven secondary and tertiary centers in Korea. Eligible subjects were < 20 years of age and had records on the presence or absence of DKA at the time of T1DM diagnosis. DKA severity was categorized as mild, moderate, or severe. Data were collected on age, height, body weight, pubertal status, family history of diabetes, delayed diagnosis, preceding infections, health insurance status, and parental education level. A total of 361 patients (male 46.3%) with T1DM were included. Overall, 177 (49.0%) patients presented with DKA at T1DM diagnosis. Risk factors predicting DKA at T1DM diagnosis were age ≥ 12 years, lower serum C-peptide levels, presence of a preceding infection, and delayed diagnosis. Low parental education level and preceding infection increased the severity of DKA. These results suggest that alertness of the physician and public awareness of diabetes symptoms are needed to decrease the incidence and severity of DKA at T1DM diagnosis.

Pediatric Goiter: Can Thyroid Disorders Be Predicted at Diagnosis and in Follow-Up?

OBJECTIVE: To investigate the prevalence of thyroid dysfunction, autoimmune thyroid disease (AITD), and simple goiter at goiter diagnosis, and to analyze the natural course of simple goiter and predictors for progression to AITD and/or thyroid dysfunction. STUDY DESIGN: In total, 939 patients (770 females, 5.0-17.9 years) with goiter were reviewed retrospectively. Anthropometrics, pubertal status, goiter grade, and family history (FH) of thyroid disease were investigated. Simple goiter was defined as euthyroid goiter without pathologic cause, after excluding AITD and isolated nonautoimmune hyperthyrotropinemia (iso-NAHT). RESULTS: At diagnosis, 36.9% of children showed thyroid dysfunction and/or AITD (euthyroid AITD [9.9%], hyper- or hypothyroid AITD [18.4%], iso-NAHT [8.6%]). Risk for subsequent medication was higher in euthyroid AITD than simple goiter (20.4% vs 0.3%, P < .001). Hashimoto thyroiditis (HT) and iso-NAHT developed in 5.2% and 6.6% of patients initially diagnosed with simple goiter during the median 2.0-year follow-up. Compared with the persistent simple goiter group, the HT group had greater FH (54.8% vs 23.6%) and unchanged or increasing goiter size (89.3% vs 71.8%), and the iso-NAHT group had a higher proportion of patients within the upper tertile range of baseline thyrotropin levels (71.8% vs 24.9%) and unchanged or increasing goiter size (86.8% vs 71.8%; all P < .05). CONCLUSIONS: Thyroid disorders were detected in one-third of pediatric patients presenting with goiter. The higher risk for thyroid dysfunction needing medication in patients with euthyroid AITD emphasizes the importance of autoantibody evaluation at diagnosis. During simple goiter follow-up, progression to HT or iso-NAHT occurs, especially in patients with FH or persistent goiter.

Cerebellar vermis hypoplasia in CHARGE syndrome: clinical and molecular characterization of 18 unrelated Korean patients.

CHARGE syndrome (OMIM 214800) is a rare autosomal-dominant congenital malformation syndrome that results from haploinsufficiency of the chromodomain helicase DNA-binding protein 7 (CHD7). We performed a phenotypic characterization and genetic analysis of CHD7 in 18 Korean patients with CHARGE syndrome. Eighteen unrelated Korean patients (10 females and 8 males; age range 0.0-19.6 years) with CHARGE syndrome were enrolled. Clinical data were collected by retrospective review of medical records. A serial analysis via sequencing and multiple ligation-dependent probe amplification of CHD7 was performed to determine the molecular genetic spectrum of the patients. The prevalence of cardinal symptoms was as follows: coloboma (13/18, 72.2%), heart defects (13/18, 72.2%), choanal atresia/stenosis (4/18, 22.2%), retarded growth (10/18, 55.6%), genital anomalies (15/18, 83.3%) and ear abnormalities (18/18, 100%). Five patients had cerebellar vermis hypoplasia (5/17, 29.4%) with no clinical symptoms or signs of cerebellar dysfunction. Furthermore, we identified genetic alterations in all 18 patients, including 10 novel mutations. Considering its frequency among patients with CHD7 mutations, cerebellar vermis hypoplasia may be a clinical diagnostic clue of CHARGE syndrome, although it is not included in the diagnostic criteria. And, the identification of CHD7 mutations may help the confirmative diagnosis.

Body composition and bone density reference data for Korean children, adolescents, and young adults according to age and sex: results of the 2009-2010 Korean National Health and Nutrition Examination Survey (KNHANES).

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.

Increasing incidence of type 1 diabetes among Korean children and adolescents: analysis of data from a nationwide registry in Korea.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in children and adolescents has increased worldwide. However, the epidemiology of T1DM among Korean youth has not been reported since 2001. We investigated the incidence of T1DM in Korean children and adolescents from 2012 to 2014 and compared it with data from 1995 to 2000. PATIENTS AND METHODS: Data were obtained from the National Health Insurance Service (NHIS) registry, and age- and sex-specific incidence rates were calculated per 100 000 population. RESULTS: In total, 706 patients (326 boys and 380 girls, aged <15 yr) with T1DM were registered in the NHIS during 2012-2014. The incidence rate per 100 000 population was 3.19 (95% confidence interval [CI] 2.96-3.43). We found incidence rates of 1.68, 3.16, and 4.46 in children 0-4, 5-9, and 10-14 yr, respectively. The T1DM incidence was 2.84 in boys and 3.56 in girls. A higher T1DM incidence was seen during 2012-2014 than from 1995-2000 (incidence rate ratio 2.33; p < 0.001). The incidence rate ratios between 1995-2000 and 2012-2014 were 2.31, 2.20, and 2.27 in children 0-4, 5-9, and 10-14 yr, respectively. The annual increase in T1DM incidence was 5.6% (95% CI 5.0-6.3%) between 1995 and 2014. CONCLUSIONS: We observed a significant increase in the T1DM incidence. This increase was higher in boys than in girls, and was highest in children aged 0-4 yr. Studies are needed to evaluate the long-term epidemiological trend of T1DM incidence.

Risk factors for low vitamin D status in Korean adolescents: the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009.

OBJECTIVE: To evaluate the prevalence of vitamin D deficiency and predictors for low vitamin D status in Korean adolescents living between latitudes 33° and 39° N. DESIGN: A descriptive cross-sectional study. SETTING: Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2009. SUBJECTS: A total of 1510 healthy adolescents aged 12-18 years (806 male, mean age 14.7 years) participated. Possible predictors for low vitamin D status (log-transformed 25-hydroxyvitamin D (25(OH)D) concentrations) were evaluated. RESULTS: The prevalence of vitamin D deficiency (25(OH)D<20 ng/ml) was 89.1% in spring, 53.7% in summer, 63.9% in autumn and 90.5% in winter. Winter season, older age, higher education level reached, being female, being obese, a lack of vitamin D supplementation, lower milk consumption (0-<200 ml/d) and a lack of physical activity were unadjusted predictors (all P < 0.05). Multiple linear regression analysis showed that winter season (P < 0.001), higher education level (P < 0.001) and a lack of vitamin D supplementation (P = 0.012) were independent predictors for low vitamin D status. The modifying effect of season on the association between vitamin D supplement use and vitamin D status was significant (P < 0.001). CONCLUSIONS: Vitamin D deficiency was highly prevalent in Korean adolescents, especially those in higher school grades. Vitamin D supplementation may contribute to maintain a better vitamin D status with lower seasonal variation. Further studies are required to determine optimal vitamin D intakes to maintain sufficient vitamin D status for Korean adolescents.

Inverse relationship between vitamin D status and insulin resistance and the risk of impaired fasting glucose in Korean children and adolescents: the Korean National Health and Nutrition Examination Survey (KNHANES) 2009-2010.

OBJECTIVE: To investigate whether low vitamin D status was related to insulin resistance (IR) or impaired fasting glucose (IFG) in Korean adolescents, after adjusting for total body fat mass (FM). DESIGN: A cross-sectional study. SETTING: Korea National Health and Nutrition Examination Survey (KNAHNES) 2009-2010. SUBJECTS: In total, 1466 participants (769 males) aged 10-19 years were assessed for serum 25-hydroxyvitamin D (25(OH)D) levels, for FM by whole-body dual-energy X-ray absorptiometry and for IR by homeostasis model assessment (HOMA-IR) after an 8 h fast. RESULTS: Age-, sex-, season- and physical-activity-adjusted regression models showed that serum 25(OH)D levels were significantly related to markers of adiposity (P = 0.016 for FM (g), P = 0.023 for FM (%) and P = 0.035 for fat mass index). When the participants were stratified into three 25(OH)D categories (<37.5 nmol/l (n 553), 37.5 to < 50 nmol/l (n 543) and ≥ 50 nmol/l (n 370)), significantly decreasing trends were observed for fasting insulin (all P < 0.001), HOMA-IR (all P < 0.001) and the odds ratios for IFG (all P for trend < 0.05) from the lowest to the highest 25(OH)D category, after adjustments for age, sex, physical activity and all markers of adiposity. In the multivariate logistic regression analysis, the likelihood of participants in the lowest serum 25(OH)D category having IFG was 2.96-3.15 compared with those in the highest 25(OH)D category (all P < 0.05). CONCLUSIONS: There was a significant inverse relationship between vitamin D status and IR and the risk of IFG, independent of adiposity, in Korean adolescents.

Tumor origin and growth pattern at diagnosis and surgical hypothalamic damage predict obesity in pediatric craniopharyngioma.

Severe obesity is a major problem in pediatric craniopharyngioma. We investigated whether tumor origin, growth pattern, and surgical damage predict obesity in pediatric craniopharyngioma. Subjects were 58 patients (30 males) with no tumor recurrence during the first postoperative 18 months. Preoperative hypothalamic involvement was classified into no (pre_G0, n = 19), little (pre_G1, n = 21), and severe (pre_G2, n = 18) involvement groups based on sub- or supradiaphragmatic tumor origin and growth patterns. Postoperative hypothalamic involvement was classified into no (post_G0, n = 4), minimal (post_G1, n = 19), and significant (post_G2, n = 35) involvement groups according to follow-up imaging. The prevalence of obesity increased from 13.2 % at diagnosis (mean age = 8.1 years) to 37.9 % at last follow-up (mean duration = 9.1 years). Only the body mass index (BMI) Z-score increment of the first postoperative year (first-year ΔBMI_Z) was significant (P = 0.007). Both the preoperative BMI_Z (P = 0.001) and the first-year ΔBMI_Z (P = 0.017) showed an increasing trend from the pre_G0 to pre_G1 to pre_G2 group. For the 40 patients with pre_G0 or pre_G1, the first-year ΔBMI_Z was higher in the post_G2 group than the post_G1 group (0.02 ± 0.91 vs. 0.89 ± 0.72, P = 0.003). Tumor origin and growth pattern affect preoperative BMI_Z and postoperative weight gain. Despite little or no hypothalamic involvement at diagnosis, surgical damage contributes to postoperative weight gain in patients with craniopharyngioma.

Adequate vitamin D status and adiposity contribute to bone health in peripubertal nonobese children.

The dietary reference intake (DRI) of vitamin D for Korean children was reduced from 400 IU/day in 2005 to 200 IU/day in 2010. We evaluated the risk factors for low 25-hydroxyvitamin D [25(OH)D] status and its relationships with bone health in peripubertal nonobese children living in Seoul or Gyeonggi-do. One hundred children (9.3 ± 1.9 years, 71 prepubertal, 45 boys) participated in the winter (n = 38, December through March) and summer (June through September). Bone mineral content (Z_BMC), fat mass (Z_FM), lean mass (Z_LM), and bone mineral density for the total body (Z_TB) and lumbar spine (Z_L1-4) were measured using dual-energy X-ray absorptiometry. Twenty-nine percent of children (47.4 % in winter, 17.7 % in summer) were vitamin D deficient (25(OH)D level of <20 ng/mL). The winter season (P = 0.008) and low vitamin D intake (P = 0.044) were associated with low 25(OH)D level. The 25(OH)D level correlated positively with Z_BMC (P = 0.040), Z_TB (P = 0.027), and Z_L1-4 (P = 0.045) independently of sex, puberty, Z_FM, Z_LM, physical activity level, and calcium intake. Z_FM correlated independently with Z_BMC (P < 0.001), Z_TB (P = 0.037), and Z_L1-4 (P < 0.001). In conclusion, almost half of peripubertal nonobese children were vitamin D deficient in winter. Adequate vitamin D status and adiposity contributed to good bone health in nonobese children. Considering the beneficial effects of adequate vitamin D status on bone health, the current DRI may be insufficient for preventing vitamin D deficiency in winter among Korean children.

Monozygotic twin discordant for Down syndrome: mos 47,XX,+21/46,XX and 46,XX.

Monozygotic twins, developed from a single zygote, are almost identical in clinical phenotype and concordant karyotypes. Monozygotic twins with discordant karyotypes are thought to be quite rare. Here, we report monochorionic-diamniotic twins discordant for Down syndrome. On findings of prenatal ultrasonography, nuchal translucency thickness was different between twins, and suggested that one of the twins was at high risk for having chromosomal abnormalities including Down syndrome. The twins were monochorionic-diamniotic; therefore, chorionic villi sampling of the common placenta was performed. The karyotype of the chorionic villi cells was 46,XX, and pregnancy was maintained. After delivery, dysmorphic clinical features suggesting Down syndrome were found in one of the twins, while the other twin showed a morphologically normal appearance. Karyotypes of peripheral blood leukocytes were repeatedly normal in the dysmorphic twin; however, the karyotype of skin fibroblasts from the dysmorphic twin indicated Down syndrome mosaicism; 47,XX,+21[99]/46,XX[2]. The karyotype of skin fibroblasts from the morphologically normal twin was 46,XX. Monozygosity of the twins was confirmed by a short tandem repeat analysis using 16 polymorphic markers. A mitotic nondisjunction followed by the twinning would explain the discordant karyotypes between monozygotic twins.

Latency of intracranial germ cell tumors and diagnosis delay.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Influence of body mass index on the growth hormone response to provocative testing in short children without growth hormone deficiency.

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for one's age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.

Growth after hematopoietic stem cell transplantation in children with acute myeloid leukemia.

Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth.