Kyoung Soon Cho

Endocrine Complications after Hematopoietic Stem Cell Transplantation during Childhood and Adolescence

Long-term survivors of hematopoietic stem cell transplantation (HSCT) during childhood and adolescence are at risk of developing endocrine complications. The purpose of this study was to evaluate the long-term endocrine complications and their associated risk factors among such patients. We reviewed the data from 111 patients (59 males and 52 females) who underwent HSCT at the mean age of 8.3±4.1 yr. Thirty patients (27.0%) had growth impairment, and seven (21.2%) out of 33 patients who attained final height reached final height below 2 standard deviation (SD). The final height SD score of the patients conditioned with total body irradiation (TBI) was significantly lower than that of the patients conditioned without TBI (-1.18±1.14 vs. -0.19±0.78, P=0.011). Thirteen patients (11.7%) developed hypothyroidism (11 subclinical, 2 central) 3.8±1.8 (range 1.6-6.2) yr after HSCT. Nineteen (65.5%) out of 29 females had evidence of gonadal dysfunction, and 18 (64.3%) out of 28 males had evidence of gonadal dysfunction. The risk for gonadal dysfunction was significantly higher in females conditioned with busulfan/cyclophosphamide (P=0.003). These results suggest that the majority of patients treated with HSCT during childhood and adolescence have one or more endocrine complications. Therefore, multiple endocrine functions should be monitored periodically after HSCT until they reach adult age.

Factors Related to Decreased Bone Mineral Density in Childhood Cancer Survivors

The risk of osteoporosis or osteopenia is known to increase after childhood cancer treatment. The purpose of this study was to evaluate patterns of bone mineral density (BMD) and to identify factors related to the decreased BMD in childhood cancer survivors. We studied 78 patients (34 boys, 44 girls) treated for childhood cancer. Twenty (25.7%) patients had lumbar BMD (LBMD) standard deviation score (SDS) lower than -2. Nineteen (24.4%) patients had femur neck BMD (FNBMD) SDS lower than -2. The patients treated with hematopoietic stem cell transplantation had lower LBMD SDS (-1.17 ± 1.39 vs -0.43 ± 1.33, P = 0.025). The risk of having LBMD SDS < -2 was higher in the patients treated with glucocorticoid (GC) for graft-versus-host disease (GVHD) (36.6% vs 13.5%; odds ratio [OR], 3.7; P = 0.020). In multivariate logistic regression analysis, longer duration of GC treatment for GVHD (OR, 1.12; 95% confidence interval [CI], 1.05-1.20) and lower body mass index (BMI) SDS (OR, 0.59; 95% CI, 0.36-0.95) were associated with decreased LBMD SDS. These findings suggest that prolonged GC use and reduction in BMI are risk factors for decreased BMD in childhood cancer survivors. Anticipatory follow-up and appropriate treatment are necessary, especially for the patients with risk factors.

Serum ferritin level is higher in male adolescents with obesity: results from the Korean National Health and Nutrition Examination Survey 2010.

Purpose Previous reports show an association between high serum ferritin levels and metabolic syndrome (MS) in adults. In adolescents, little information is available with obesity and serum ferritin levels. Methods This is a cross-sectional study. Data were obtained from the 5th Korean National Health and Nutrition Examination Survey (K-NHANES) conducted during 2010 by the Korean Ministry of Health and Welfare. A total of 849 subjects aged 10-18 years participated in the 2010 survey. A body mass index (BMI) ≥95th percentile for age and sex or a BMI ≥25 was used to diagnose as obesity. Results The weighted prevalence of obesity was 13.4% (62/462) in male and 8.5% (33/387) in female. We observed significantly higher serum ferritin in male than in female (mean±standard error [SE], 50.5±2.3 µU/L vs. 30.6±1.3 µU/L; P<0.0001). In male, serum ferritin is positively correlated with age (P<0.0001). White blood cell (WBC) count, serum fasting blood sugar, triglyceride (TG), total cholesterol, low-density lipoprotein, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), systolic and diastolic blood pressure, and ferritin levels were higher and high-density lipoprotein (HDL) were lower in the obesity than in the normal group. In female adolescents, WBC count, TG, insulin, and HOMA-IR were higher and HDL were lower in the obesity than in the normal group. In male, serum ferritin levels showed positive association with obesity (β=21.196, P=0.016). Conclusion Serum ferritin levels appear to be associated with obesity in Korean male adolescents.

Insulin Resistance of Normal Weight Central Obese Adolescents in Korea Stratified by Waist to Height Ratio: Results from the Korea National Health and Nutrition Examination Surveys 2008–2010

Background. To evaluate insulin resistance of normal weight central obese 13–18-year-old male and female adolescents stratified by waist to height ratio (WHR). Methods. Data were obtained from the Korea National Health and Nutrition Examination Survey (K-NHANES) conducted during 2008–2010. Central obesity was defined as that in the upper quartile of age and sex specific WHR. Subjects were classified into no central obesity normal weight (NW), central obesity normal weight (CONW), no central obesity overweight (OW), and central obesity overweight (COOW). Results. The prevalence of CONW was 9.6% (83/832) in female and 7.0% (61/909) in male. CONW showed higher levels of insulin (P < 0.006), HOMA-IR (P < 0.006), and ALT (P < 0.001) than NW in female. CONW had higher levels of insulin (P < 0.0001), HOMA-IR (P < 0.0001), and WBC count (P < 0.021) and lower level of HDL (P < 0.0001) than NW in male. WHR and BMI had similar significant correlations with MS components. CONW showed 2.5 times (95% confidence interval, 1.21–5.00) more likelihood to have high insulin resistance than NW in male. Conclusions. Screening for central obesity using WHR in clinical setting is recommended.

Urinary markers in the early stage of nephropathy in patients with childhood-onset type 1 diabetes

BackgroundThe aim of this study was to evaluate the association of a urinary tubular marker, liver-type fatty acid binding protein (L-FABP) and an inflammatory marker, serum/urinary YKL-40, with albuminuria in patients with childhood-onset type 1 diabetes (T1D).MethodsTwenty-nine patients with childhood-onset T1D and 32 controls were enrolled. Serum and urinary concentrations of YKL-40 and urinary concentrations of L-FABP were measured.ResultsThe serum levels of YKL-40 were not significantly different between the control group and the patient groups. However, the levels of urinary YKL-40/creatinine (Cr) were higher in the patients, even those with normoalbuminuria than in the controls (p < 0.001). The levels of urinary L-FABP/Cr were not different between the control group and the patient groups. However, the level of urinary L-FABP/Cr in the microalbuminuria group was higher than that in the normoalbuminuria group (p = 0.03). There were no associations between the levels of urinary albumin-to-creatinine ratio and urinary L-FABP/Cr or YKL-40/Cr. However, the urinary L-FABP/Cr level was significantly correlated with the hemoglobin A1C level (p = 0.005) and the urinary YKL-40/Cr level (p = 0.043).ConclusionsUrinary L-FABP/Cr and YKL-40/Cr may reflect renal injury in early stages of nephropathy in patients with childhood-onset T1D, even in the normoalbuminuric state.

Relationships of physical fitness and obesity with metabolic risk factors in children and adolescents: Chungju city cohort study.

Purpose The purpose of this study was to investigate the relationships of physical fitness and obesity with metabolic risk factors in children and adolescents. Methods This cohort study was conducted in Chungju city, South Korea. Total 843 subjects were enrolled, including 193 elementary school 4th grade male (E4M), 189 elementary school 4th grade female (E4F) and 461 male-middle school students (M1M). The subjects were also classified into 2 groups by body mass index; normal weight (NW) group and overweight included obesity (OW/OB) group. Physical fitness was measured by shuttle run (cardiorespiratory fitness, CRF), sit and reach (flexibility), handgrip strength (muscular strength) and stand long jump (agility). Results The prevalence of OW/OB was respectively 33.7% (65 of 193) among E4M, 28.6% (54 of 189) among E4F, and 28.0% (129 of 461) among M1M. Hematocrit, white blood cell, triglyceride, low-density lipoprotein, insulin, homeostasis model assessment of insulin resistance, systolic and diastolic blood pressure were higher, while high-density lipoprotein were lower in the OW/OB group than in the NW group. The OW/OB group presented significantly lower CRF (P<0.01) and lower agility, but higher muscular strength compared with NW group. CRF was negatively correlated with obesity indices and metabolic risk factors. After adjustments for potential confounders, odds ratios for 4th–5th grade CRF of OW/OB compared NW in the E4M, E4F, M1M, were 7.38 (95 % CI, 3.24–16.83), 4.10 (95% CI, 1.83–9.18), 16.06 (95% CI, 8.23–31.00) (P<0.01). Conclusion Our study has shown that CRF has negative correlation with OW/OB in children and adolescents of Chungju city. We suggest that improvement of CRF through regular physical activity would be an important method for reducing the metabolic risks of childhood obesity.

Serum lipid profiles and glycemic control in adolescents and young adults with type 1 diabetes mellitus

Purpose We aimed to investigate serum lipid profiles and glycemic control in adolescents and young adults with type 1diabetes mellitus (T1DM). Methods This cross-sectional study included 29 Korean young adults and adolescents with T1DM. The median age was 17 years (range, 10-25 years) and 18 (62.1%) were female. We compared the lipid profiles of patients with dyslipidemia and those without dyslipidemia. Correlations between glycosylated hemoglobin (HbA1c) and lipid profiles (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglyceride [TG]) were determined by linear regression analysis. Results Of the 29 patients with T1DM, 11 (37.9%) were classified as having dyslipidemia due to the following lipid abnormality: TC≥200 mg/dL in 8 patients, LDL-C≥130 mg/dL in 4 patients, TG≥150 mg/dL in 2 patients, and HDL-C≤35 mg/dL in 2 patients. Compared to patients without dyslipidemia, patients with dyslipidemia were more likely to have higher values of HbA1c (median, 10.6%; range, 7.5%-12.3% vs. median, 8.0%; range, 6.6%-10.0%; P=0.002) and a higher body mass index z score (median, 0.7; range, -0.57 to 2.6 vs. median, -0.4; range, -2.5 to 2.2; P=0.02). HbA1c levels were positively correlated with TC (P=0.03, R2=0.156) and TG (P=0.005, R2=0.261). Conclusion A substantial proportion of adolescents and young adults with T1DM had dyslipidemia. We found a correlation between poor glycemic control and poor lipid profiles in those patients.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patients blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

Association between serum alanine aminotransferase level and obesity indices in Korean adolescents

Purpose To analyze the correlation between serum alanine aminotransferase (ALT) and obesity indices including body mass index (BMI), body fat percentage (BFP), total fat mass (FM), truncal fat mass (TFM), waist circumference (WC), and waist-to-height ratio (WHtR) in Korean adolescents. Methods This was a cross-sectional study based on data derived from the 2010-2011 Korean National Health and Nutrition Examination Surveys (KNHANES). Subjects were Korean adolescents aged 10-18 years (871 total; 475 boys and 396 girls) who participated in KNHANES. Results In both sexes, BMI, FM, TFM, WC, and WHtR were higher when ALT levels were in the 4th quartile. In boys, there was a significant positive correlation between ALT level and BMI, BFP, FM, TFM, WC, and WHtR (r=0.55, P<0.0001 for BMI; r=0.52, P<0.0001 for BFP; r=0.58, P<0.0001 for FM; r=0.61, P<0.0001 for TFM; and r=0.56, P<0.0001 for WC; r=0.62, P<0.0001 for WHtR), and the correlation coefficient was higher than that in girls. Conclusion Our results suggest a significant positive association between serum ALT level and obesity indices in male adolescents.

The association between skeletal maturation and adrenal androgen levels in obese children and adolescents

Purpose This study aimed to investigate the association between skeletal maturation and adrenal androgen levels in obese children and adolescents. Methods Fifty-three children and adolescents (aged 7–15 years) diagnosed as obese or overweight were investigated. Anthropometric measurements, bone age (BA) determination, serum biochemical analyses, and hormonal measurements were performed. The difference between BA and chronological age (BA–CA, dBACA) was calculated and used to represent the degree of advanced skeletal maturation. Results Thirty-one subjects were classified into the obese group and 22 subjects into the overweight group. Insulin resistance as calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly higher in the obese group than in the overweight group (4.03±2.20 vs. 2.86±1.11, P=0.026). The skeletal maturation of the obese group was advanced, but the dBACA did not differ between the obese and overweight groups statistically (1.43±1.35 vs. 0.91±1.15, P=0.141). Serum dehydroepiandrosterone sulfate (DHEA-S) levels were significantly higher in subjects with dBACA>1 compared to those with dBACA≤1 (104.3±62.2 vs. 59.6±61.0, P=0.014). Correlation analyses demonstrated that dBACA was positively correlated with body mass index standard deviation scores (r=0.35, P=0.010), fasting insulin (r=0.36, P=0.009), HOMA-IR (r=0.30, P=0.031), and insulin-like growth factor-binding protein-3 (r=0.331, P=0.028). In multivariate linear regression analysis, HOMA-IR (P=0.026) and serum DHEA-S (P=0.032) were positively correlated with the degree of advanced skeletal maturation. Conclusion Advanced skeletal maturation is associated with increased insulin resistance and elevated DHEA-S levels in obese children and adolescents.