Prevalence of the Components of Metabolic Syndrome in Childhood Cancer Survivors / 임상소아혈액종양

BACKGROUND: Childhood cancer survivors have been reported to have an increased risk of prevalence of metabolic syndrome compared to the normal population. The purpose of this study was to investigate the prevalence of the components of metabolic syndrome in childhood cancer survivors in a single institute.METHODS: The study included survivors who had survived for at least 5 years after off chemotherapy without evidence of recurrence. We measured body mass index (BMI), triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, systolic and diastolic blood pressure, and fasting glucose.RESULTS: We investigated 58 childhood cancer survivors, median age 5.4 years (range, 0.1-17.2 years) at diagnosis and median follow-up time elapsed after off chemotherapy 7.4 years (range, 4.7-18.6 years). The frequency of metabolic syndrome was 3.4%. The prevalence of each component was: obesity, 17.2%; elevated TG level, 46.6%; low HDL cholesterol, 34.5%; elevated blood pressure, 1.7%; and elevated fasting glucose, 9.3%, respectively. Sixty nine percentage of survivors had at least 1 abnormal component of metabolic syndrome. The increased TG level was found more frequently in obese subjects than normal weight subjects.CONCLUSION: We observed the high incidence of increased TG level in childhood cancer survivors. It is necessary to be closely monitored the components of metabolic syndrome in childhood cancer survivors, in order to prevent them from cardiovascular diseases and improve their health outcomes.

Prevalence of the Components of Metabolic Syndrome in Childhood Cancer Survivors / 임상소아혈액종양

BACKGROUND: Childhood cancer survivors have been reported to have an increased risk of prevalence of metabolic syndrome compared to the normal population. The purpose of this study was to investigate the prevalence of the components of metabolic syndrome in childhood cancer survivors in a single institute. METHODS: The study included survivors who had survived for at least 5 years after off chemotherapy without evidence of recurrence. We measured body mass index (BMI), triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, systolic and diastolic blood pressure, and fasting glucose. RESULTS: We investigated 58 childhood cancer survivors, median age 5.4 years (range, 0.1-17.2 years) at diagnosis and median follow-up time elapsed after off chemotherapy 7.4 years (range, 4.7-18.6 years). The frequency of metabolic syndrome was 3.4%. The prevalence of each component was: obesity, 17.2%; elevated TG level, 46.6%; low HDL cholesterol, 34.5%; elevated blood pressure, 1.7%; and elevated fasting glucose, 9.3%, respectively. Sixty nine percentage of survivors had at least 1 abnormal component of metabolic syndrome. The increased TG level was found more frequently in obese subjects than normal weight subjects. CONCLUSION: We observed the high incidence of increased TG level in childhood cancer survivors. It is necessary to be closely monitored the components of metabolic syndrome in childhood cancer survivors, in order to prevent them from cardiovascular diseases and improve their health outcomes.

Asthma Development Partially Linked to Adiponectin and Leptin in Overweight Children / 소아알레르기및호흡기학회지

PURPOSE: The prevalence of asthma and obesity is increasing concomitantly, but the link between asthma and obesity is unclear. We sought to address possible roles of leptin and adiponectin in the development of asthma, and changes in pulmonary function in overweight children. METHODS: Four study groups of 61 children aged 6 to 18 years (mean age, 9.69+/-2.16) were enrolled: (1) 14 mild-to-moderate asthmatics with overweight, (2) 16 mild-to-moderate asthmatics with normal weight, (3) 16 obese subjects without asthma, and (4) 15 healthy controls. We measured biomarkers in blood, including total and allergen-specific IgE, eosinophil, eosinophilc cationic protein (ECP), leptin, adiponectin, interleukin (IL)-6, tumor necrosis factor-alpha (TNF-alpha), lipid profiles, insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3). Body mass index (BMI), antioxidants and micronutrients in a daily diet were evaluated by the questionnaire. We performed the bronchial challenge test by methacholine inhalation and free running, respectively. RESULTS: The leptin levels was apparently high, and the adiponectin level was low in the over-weight children, as depicting a significant inverse correlation between the 2 variables (R=-0.479; P<0.001). The FEV(1)/FVC ratio was low in the overweight children regardless of the presence of asthma. However, the effect of IL-6, TNF-alpha, nutrients, and other variables on asthma development in the overweight children with asthma was not verified. CONCLUSION: In this study, the levels of leptin, adiponectin or other obesity-related biomarkers were not independently associated with asthma. Therefore, it is concluded that obesity may not be an important factor in pulmonary function impairment.

Patterns of Obesity during Anti-cancer Chemotherapy in Children with Acute Lymphoblastic Leukemia

BACKGROUND: We evaluated the pattern as well as the predictive factors of obesity in children with acute lymphoblastic leukemia (ALL) according to body mass index (BMI) changes that occur during anticancer chemotherapy. METHODS: We reviewed the medical records of 58 patients who were diagnosed with ALL between 1995 and 2006 at the Department of Pediatrics at Hanyang University Hospital and Dong-A University Hospital. Five relapsed cases were excluded. The heights and weights of 55 children were measured at diagnosis, after induction, after consolidation, before maintenance and at the end of therapy. We analyzed the body mass index (BMI, kg/m(2)) for each treatment phase and evaluated the BMI differences for patients who received or did not receive cranial radiotherapy. RESULTS: The BMI increased in five children (10.4%) among the 48 children who were not obese at diagnosis. According to the treatment phase, the BMI of study patients significantly increased during induction and during chemotherapy. Even though the BMI also significantly increased according to the treatment phases in the children who underwent cranial radiotherapy, the BMI differences between patients that received or did not receive cranial radiotherapy were not statistically significant. CONCLUSION: We suggest that the risk for obesity in children with ALL should be considered even during chemotherapy. Physical activities, including physiotherapy, should be encouraged to prevent obesity, particularly during the long-term use of corticosteroids and during hospital admission.

Hypercalcemia and Extensive Osteolytic Lesion with Increased Plasma Prostaglandin E2 Level in a Child with Acute Lymphoblastic Leukemia

In this report, we present a rare case of childhood ALL with hypercalcemia and extensive osteolytic lesions. The case was a 7-year-old girl presenting with vomiting and aggravating bone pain. Radiologic examinations showed severe osteolytic lesions of the skull and extremities. Laboratory findings revealed low hemoglobin, normal WBC count with absent circulating blasts, and an increased serum calcium level. Serum intact PTH and 1,25-(OH)2 vitamin D3 levels were below the normal ranges and parathyroid hormone-related peptide (PTHrP) was not detected, whereas serum levels of prostaglandin E2 were elevated. The hypercalcemia resolved with specific antileukemic chemotherapy along with supportive care. The elevated plasma prostaglandin E2 levels decreased slightly after complete remission with induction chemotherapy. These findings suggest that increased plasma prostaglandin E2 levels may be one of the pathogenetic mechanisms responsible for the occurrence of hypercalcemia in this patient.

Analysis of the Inquiry Types of the Pediatric Endocrinologic Diseases Counseled on the Internet / 대한소아내분비학회지

PURPOSE: On account of the civilization progress and popularization of the internet, we have researched the current public understandings of the pediatric endocrinologic diseases. METHODS: Analyzable 582 cases of 1,160 cases inquired by the online counsel board for the pediatric endocrinologic diseases from March of 2001 to January of 2004 were classified into four groups. RESULTS: There were 187 inquiries related to short stature. Most counsels were taken by their mothers. In the height distribution of them, under 3 percentile were 27 (21.4%). About precocious puberty, there were 82 for girls and 8 for boys of the total 110 inquiries. The number of children among 6-10 year old were 62. The main subject matter of inquiry accounted for the great majority as 67 cases was about breast budding. And there were 117 inquiries related to childhood diabetes. The number of children among 1-5 year old were 43 (49.4%). Lastly, there were 149 inquiries related to the thyroid diseases. The number of children under 1 year old were 55 (45.8%). CONCLUSION: Considering the most cases of the stature under 50 percentile on the current Korean growth curve begun since 1998, a present phase of quite competition of the stature was recognized. And it could be possible to say that the maternal factor for short stature seems more important than the paternal factor, because our data show that the short stature mothers of the short stature children is two folds more than the short stature fathers of them.

Factors Related to Complications of Childhood Obesity / 대한소아내분비학회지

PURPOSE: Childhood obesity is associated with complications such as hyperinsulinemia/insulin resistance, dyslipidemia and fatty liver. The aims of this study were to evaluate the difference of measurements between obese and normal weight children and to investigate the factors related to complications of obesity. METHODS: The body mass index (BMI), trunk and total fat percent, lipid profiles, ALT, AST, leptin, LH, FSH, fasting insulin, glucose, IGF-1, IGFBP-3 were measured in 97 children (49 obese children and 48 non-obese controls). We calculated G/I ratio, loginsuin, HOMA-IR, logHOMA-IR, and QUICKI and evaluated the relationship between each anthropometric data and metabolic data. RESULTS: Hyperinsulinemia, dyslipidemia and abnormal ALT showed high prevalence in obese children. In obese, BMI was correlated with G/I ratio (r=-0.309, P<0.05), loginsuin (r=0.381, P<0.05), logHOMA-IR (r= 0.342, P<0.05), QUICKI (r=-0.343, P<0.05), ALT (r=0.451, P<0.01)) and AST (r=0.289, P<0.05). Serum insulin level had positive correlation with BMI (r=0.345, P<0.01), serum triglyceride (r=0.332, P<0.05) and all insulin resistance indices (P<0.01). Serum leptin levels were significantly correlated with BMI (r=0.555, P<0.01), trunk (r=0.463, P<0.01)) and total (r=0.506, P<0.01) fat percent, LDL (r=0.350, P<0.05), total cholesterol (r=0.297, P<0.05). CONCLUSION: BMI is valuable for predicting insulin resistance and prevalence of abnormal ALT or AST. Monitoring of insulin level is helpful to assess the morbidities of obesity. Also, serum leptin level might be an important predictor of obesity.

The Relationship between Insulin-like Growth Factor Binding Protein-3 Promoter Polymorphism and Growth / 대한소아내분비학회지

PURPOSE: The variability in insulin-like growth factor binding protein-3 (IGFBP-3) levels is related to polymorphic variants of the promoter region of the gene. The most common single nucleotide polymorphism of IGFBP promoter region is -202 locus. In vitro, significantly higher promoter activity of the A allele at the -202 locus compared with the C allele, consistent with the relationship observed between genotype and circulating IGFBP-3 was documented. The polymorphic variation occurs frequently and may influence GH responsiveness, somatic growth, but the effects of IGFBP-3 promoter polymorphism on growth in children are unknown. METHODS: RFLP genotyping of the -202 single nucleotide polymorphism was performed in 33 Korean children who visited our clinic for evaluation of their growth. The serum levels of IGF-I and IGFBP-3 were compared according to genotyping. RESULTS: Height SDS of subjects was -1.48+/-1.10. 11 of 33 children (33%) were heterozygous AC and the others are homozygous AA in genetic distribution, but no homozygous CC was detected. C allele frequency was 16.7%. There were no significant differences in height, body mass index, serum IGF-I and IGFBP-3 levels between AC and AA groups. CONCLUSION: The effects of IGFBP-3 promoter polymorphism on growth at the -202 locus deserve investigation because there is no CC and the children were relatively short in this study.

A Sustained Release Human Growth Hormone (LB03002):Efficacy and Safety Following Six-month Treatment in Children with Growth Hormone Deficiency (GHD) / 대한소아내분비학회지

BACKGROUND: LB03002[somatropin(rDNA origin) for injectable suspension] is a sustained release formulation of human growth hormone to be administered by once-a-week subcutaneous injections. Less frequent administration could provide a considerable improvement on compliance and convenience. OBJECTIVE: To determine the efficacy and safety of a LB03002 administered in children with GHD once weekly for 6 months. DESIGN: Open-label, active-controlled, randomised, parallel group, phase II study. PATIENTS: A total of forty-two naive or previously treated, pre-pubertal children with GHD, confirmed by two different GH provocation tests, were randomised and received either LB03002(0.3 or 0.5 mg/kg/week) or Eutropin(TM)(daily rhGH, 0.3 mg/ kg/week divided 6 times a week) for 6 months. RESULTS: The pre-treatment(HV0) and 6-month annualised height velocity(HV6) are shown(mean+/-SD) in the table below: ----------------------------------------------------------------------- LB03002 LB03002 EutropinTM 0.3 mg/kg/week 0.5 mg/kg/week 0.3 mg/kg/week ----------------------------------------------------------------------- N 10 13 13 HV0 3.1+/-1.0 3.9+/-1.5 3.0+/-1.1 HV6 9.3+/-2.3 10.2+/-2.3 11.1+/-2.5 ----------------------------------------------------------------------- Mean IGF-I and IGFBP-3 levels were significantly elevated from baseline values in all the study groups. LB03002 at all dose groups was safe and well tolerated. No clinically relevant adverse events or abnormal laboratory parameters were observed and there were no remarkable differences between groups or changes over time within groups regarding parameters for glucose and lipid metabolism including fasting glucose and haemoglobin A1c. Injection site reactions were mostly mild to occasionally moderate and resolved within 2 to 3 days post-dose without intervention. CONCLUSIONS: Treatment with LB03002 by weekly administration of the doses tested in the study resulted in comparable safety and efficacy to daily rhGH in pre-pubertal children with GHD.

The Relationship between BMI, Height and Leptin, Insulin, IGF-I and IGFBP-3 in Obese Children / 대한소아내분비학회지

PURPOSE: The prevalence and severity of childhood obesity are increasing rapidly worldwide. Spontaneous and stimulated growth hormone (GH) secretion are impaired in obesity. However, despite the low GH levels, normal or increased insulin-like growth factor-I (IGF-I) levels have been observed in obese subjects. Growth velocity is commonly normal or increased in obese children. As for the possible mechanisms underlying these observations, overnutrition, chronic hyperinsulinemia and increased free IGF-I have been suggested. To explain the possible mechanisms by which obese children are taller than normal weight children, we have compared height, leptin, insulin, IGF-I and IGF binding protein-3 (IGFBP-3) with body mass index and studied the relationship among these parameters in obese and control group. METHODS: Auxological and endocrine evaluation were performed in 33 obese children (18 boys and 15 girls) and 47 non-obese children (24 boys and 23 girls) at Hanyang University Hospital from Jan. 1999 to Dec. 2000. Obesity was defined as a body mass index (BMI) greater than the 95th percentile for age and sex. Fasing blood samples were taken for the measurement of serum leptin, insulin, IGF-I and IGFBP-3 by radioimmunoassay. RESULTS: The serum concentrations of leptin, insulin, IGF-I and IGFBP-3 were significantly higher in obese children than those in non-obese children. The serum concentrations of leptin (r=0.751, P=0.000), insulin (r=0.746, P=0.000) and IGF-I (SDS) (r=0.747, P=0.000) showed positive correlation to BMI. And the serum concentrations of IGFBP-3 showed positive correlation to BMI with low correlation coefficient respectively (r=0.275, P=0.015). The serum concentration of insulin correlated to that of IGF-I (SDS) positively (r=0.585, P=0.000). CONCLUSION: This study suggest that increased sensitivity of GHR modulated by chronic hyperinsulinemia and increased circulating IGF-I produced by accumulated adipose tissue may enhance the growth in obese children.

A Case of Mayer-Rokitansky-Kuster-Hauser (MRKH) Syndrome with Amenorrhea and Sexual Precosity / 대한소아내분비학회지

The Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is comprised of vaginal atresia with other variable Mullerian duct abnormalities. Its features include an absent or very short vagina and a uterus that can be absent or immaturely formed. Female with MRKH syndrome have functioning ovaries, normal external genitalia and the typical 46, XX, karyotype. MRKH syndrome is the second most common cause of primary amenorrhea, usually remains undetected until the patient presents with primary amenorrhea despite normal sexual female development. We report a case of MRKH syndrome, associated with ovarian follicular cyst, in a 14-years-old girl who visited for primary amenorrhea and sexual precosity.

A Case of Sertoli Cell Tumor Presented with Sexual Precosity / 대한소아내분비학회지

Some sexual differentiation disorders are associated with gonadal neoplasia and increased incidence of testicular tumors has been discribed in the patients with, XY gonadal dysgenesis. The incidence of testicular tumors in infants and children are rare, representing only 1% of all pediatric solid tumors. In general, gonadal stromal tumors are one of the most characteristic endocrine tumors of the testis, endocrine activity occurs in at least 10-20%, among them Leydig cell tumors and Sertoli cell tumors are clinically important. Although the exact pathogenesis is unknown, endocrine activity due to estrogen secretion can be manifested clinically with gynecomastia or precocious puberty. We experienced and reported a child who visited for sexual precocity and had XY gonadal dysgenesis with Sertoli cell tumor.

Growth Assesssment / 대한내분비학회지

No abstract available.

Changes in High Levels of 17 alpha-Hydroxyprogesterone at Neonatal Screening / 대한소아내분비학회지

PURPOSE:There are some cases of false positive in neonatal screening for congenital adrenal hyperplasia. To understand its significance of the increased 17 alpha-hydroxyprogesterone(17 alpha-OHP) levels in the cases of positive result, we followed its levels during infancy. METHODS:From July 1997 to June 1998, totally 1,730 babies were screened for congenital adrenal hyperplasia(CAH) measuring 17 alpha-hydroxyprogesterone(17 alpha- OHP) using an enzyme immunoassay(EIA) on dried blood spots. In infants of positive result, the radioimmunoassay(RIA) was used measuring 17 alpha-OHP in serum. And we followed up the levels of 17 alpha-OHP during infancy. Cortisol and ACTH were also measured and followed up in the morning simultaneously. RESULTS:No CAH was detected during the study period. With the 13 ng/mL cutoff limit for 17 alpha-OHP before March 1998, the recall rate was 3.09%. With the 20 ng/mL cutoff limit after March 1998, the recall rate was decreased to 1.58%. Follow-up of the high levels of 17 alpha-OHP in positive cases showed a sharply decreased curve according to age. CONCLUSION: In clinically normal neonates, the high levels of 17 alpha-OHP at screening decreased continuously during infancy.

Changes in High Levels of 17 alpha-Hydroxyprogesterone at Neonatal Screening / 대한소아내분비학회지

PURPOSE:There are some cases of false positive in neonatal screening for congenital adrenal hyperplasia. To understand its significance of the increased 17 alpha-hydroxyprogesterone(17 alpha-OHP) levels in the cases of positive result, we followed its levels during infancy. METHODS:From July 1997 to June 1998, totally 1,730 babies were screened for congenital adrenal hyperplasia(CAH) measuring 17 alpha-hydroxyprogesterone(17 alpha- OHP) using an enzyme immunoassay(EIA) on dried blood spots. In infants of positive result, the radioimmunoassay(RIA) was used measuring 17 alpha-OHP in serum. And we followed up the levels of 17 alpha-OHP during infancy. Cortisol and ACTH were also measured and followed up in the morning simultaneously. RESULTS:No CAH was detected during the study period. With the 13 ng/mL cutoff limit for 17 alpha-OHP before March 1998, the recall rate was 3.09%. With the 20 ng/mL cutoff limit after March 1998, the recall rate was decreased to 1.58%. Follow-up of the high levels of 17 alpha-OHP in positive cases showed a sharply decreased curve according to age. CONCLUSION: In clinically normal neonates, the high levels of 17 alpha-OHP at screening decreased continuously during infancy.

Conginital Adrenal Hyperplasia

No abstract available.

A Case of Cerebral Gigantism(Sotos Syndrome) / 대한소아내분비학회지

Cerebral gigantism(Sotos syndrome) is a growth disorder that consists of large size at birth, rapid early growth rate with accompanying advanced bone age, acromegalic features, and developmental delay. Clumsiness in the absence of other abnormal neurologic findings is common. The cause is unknown. We report here a case of 238/12-year-old Sotos syndrome with final adult height above 97 percentile, abnormal brain MRI findings(large ventricles, prominent trigone, prominent occipital horn & thining of corpus callosum), clumsiness, and some behavioral problems.

A Case of Testicular Regression Syndrome / 대한소아내분비학회지

Testicular regression syndrome may be better known as vanishing testis syndrome to physicians. Such individuals are genetically male(46,XY), presenting with unilateral or bilateral absence of recognizable testis structures and absence of the Mullerian duct system. There is a wide spectrum of phenotypes depending on the stage of male embryogenesis at which testicular function ceased. We experienced a case of testicular regression syndrome presenting labial fusion at birth and report with the brief review of related literature.

A Case of Van Wyk-Grumbach Syndrome / 대한소아내분비학회지

Van Wyk-Grumbach Syndrome is an advanced sexual development in association with primary hypothyroidism. The clinical feature in this syndrome is more consistent with stimulation of the FSH receptor by the markedly elevated TSH levels. Treatment of the hypothyroidism results in a rapid return to normal of the biochemical and clinical manifestations. We experienced a case of Van Wyk-Grumbach Syndrome and report with the brief review of related literature.

A Molecular Genetic Study with EcoRII Restriction Enzyme on the Steroidogenic Acute Regulatory Protein (StAR) Gene / 대한소아내분비학회지

The molecular defect of congenital lipoid adrenal hyperplasia has been discovered to be in the transport of cholesterol into mitochondria due to defective regulatory protein called "Steroidogenic Acute Regulatory Protein (StAR)", while the enzyme P450scc itself is normal. This study with EcoRII restriction enzyme aimed at elucidating more conveniently the molecular defect in the StAR gene. The genomic DNAs were extracted from their peripheral blood. We amplified the exon 7, hot spot, of the StAR gene with 1 set of primers by Polymerase Chain Reaction (PCR). Subsequently, a PCR product corresponding to target sequence (~437 bps) from the patient and her father have been sequenced by automatic sequence analyzer. The PCR-RFLP (Restriction Fragment Length Polymorphism) analysis after restriction digestion with EcoRII restriction enzyme was also performed on 12% polyacrylamide gel electrophoresis. The mutation was identified in the exon 7 of the StAR gene, substituting C for T at codon 258, consequently replacing glutamine by stop codon. This mutation alters EcoRII restriction site. In addition, we obtained the good result of PCR-RFLP (Restriction Fragment Length Polymorphism) analysis on 12% polyacrylamide gel electrophoresis. Therefore, the PCR-RFLP (Restriction Fragment Length Polymorphism) analysis with EcoRII restriction enzyme can be easily utilized to screen carrier, diagnose the patient prenatally or postnatally.