Factors influencing growth hormone therapy effect during the prepubertal period in small for gestational age children without catch-up growth

Purpose@#Because small for gestational age (SGA) children who fail to experience catch-up growth have an increased risk of short stature in adulthood, growth hormone (GH) treatment is recommended for effective growth. In this study, we evaluated the effect of GH treatment during the prepubertal period and analyzed for correlation between GH treatment response and clinical factors in SGA children. @*Methods@#A retrospective, single-center study was conducted from 2014 to 2020. A total of 34 prepubertal children of short stature up to 4 years of age and born as SGA were enrolled. We recorded clinical data including birth data, age, weight, height, bone age (BA), and insulin-like growth factor 1 (IGF-1) levels. @*Results@#The mean gestational age and birth weight were 37.50±2.51 weeks and 2,200.00±546.79 g. At the start of GH treatment, the mean chronological age and BA were 5.54±1.73 years and 4.52±1.85 years, respectively. The height standard deviation score (SDS) (-2.47±0.45) and IGF-1 SDS (0.16±1.57) were calculated. Height velocity was 9.43±1.40 cm during the first GH treatment year and 7.63±1.16 cm during the second year (P<0.05). The treatment growth response was positively correlated with young age (P=0.047) and lower BA (P=0.049) at the start of treatment. In multiple regression analysis, IGF-1 SDS change had a significantly positive association with GH treatment response (P=0.045). @*Conclusion@#GH treatment is effective for short stature SGA children who do not experience catch-up growth. Early initiation of GH treatment improved growth outcomes. As IGF-1 SDS is positively correlated with height SDS, IGF-1 monitoring is important during GH treatment of SGA prepubertal children.

Factors influencing growth hormone therapy effect during the prepubertal period in small for gestational age children without catch-up growth

Purpose@#Because small for gestational age (SGA) children who fail to experience catch-up growth have an increased risk of short stature in adulthood, growth hormone (GH) treatment is recommended for effective growth. In this study, we evaluated the effect of GH treatment during the prepubertal period and analyzed for correlation between GH treatment response and clinical factors in SGA children. @*Methods@#A retrospective, single-center study was conducted from 2014 to 2020. A total of 34 prepubertal children of short stature up to 4 years of age and born as SGA were enrolled. We recorded clinical data including birth data, age, weight, height, bone age (BA), and insulin-like growth factor 1 (IGF-1) levels. @*Results@#The mean gestational age and birth weight were 37.50±2.51 weeks and 2,200.00±546.79 g. At the start of GH treatment, the mean chronological age and BA were 5.54±1.73 years and 4.52±1.85 years, respectively. The height standard deviation score (SDS) (-2.47±0.45) and IGF-1 SDS (0.16±1.57) were calculated. Height velocity was 9.43±1.40 cm during the first GH treatment year and 7.63±1.16 cm during the second year (P<0.05). The treatment growth response was positively correlated with young age (P=0.047) and lower BA (P=0.049) at the start of treatment. In multiple regression analysis, IGF-1 SDS change had a significantly positive association with GH treatment response (P=0.045). @*Conclusion@#GH treatment is effective for short stature SGA children who do not experience catch-up growth. Early initiation of GH treatment improved growth outcomes. As IGF-1 SDS is positively correlated with height SDS, IGF-1 monitoring is important during GH treatment of SGA prepubertal children.

Effectiveness of growth hormone therapy in children with Noonan syndrome

Purpose@#Recombinant human growth hormone (rhGH) has been used to improve growth in children with Noonan syndrome (NS). This study aimed to investigate the efficacy of rhGH therapy in Korean children with NS. @*Methods@#Seventeen prepubertal children (10 boys, 7 girls) with NS who received rhGH therapy for at least 3 years between 2008 and 2017 were included. To compare the response, age- and sex-matched children with GH deficiency (GHD; n=31) were included. Height and growth velocity before and during treatment were analyzed. @*Results@#The mean age of NS patients was 6.34±2.32 years. After treatment, the height standard deviation score (SDS) increased from -2.93±0.81 to -1.51±1.00 in patients with NS and from -2.45±0.42 to -1.09±0.47 in patients with GHD. There were no significant differences in growth velocity or change in height SDS between patients with NS and GHD. Growth velocity in the first year of treatment was higher in patients with PTPN11 mutations than those without PTPN11 mutations, but the change in height SDS was not significantly different between those 2 groups. @*Conclusion@#rhGH therapy can increase linear growth in prepubertal children with NS. The growth response between patients with NS and patients with GHD was not significantly different. Furthermore, we observed that lower doses of growth hormone have a similar effect on height compared to previous studies in patients with NS. Our study indicates that rhGH treatment is useful for growth promotion.

Clinical and radiological findings of incidental Rathke's cleft cysts in children and adolescents

PURPOSE: In the pediatric population, Rathke's cleft cysts (RCCs) are known to be an infrequent cause of headaches, visual disturbances, and pituitary dysfunction. We investigated the clinical characteristics of children in whom RCCs were incidentally discovered and evaluated whether RCCs influence the treatment response of patients with proven endocrinopathy. METHODS: A retrospective analysis was conducted in 34 patients with RCCs who were diagnosed between 2006 and 2013 at Hallym University Medical Center. Their clinical, hormonal, and imaging findings were reviewed. We evaluated the clinical outcomes of the patients with concomitant RCCs and endocrinopathy compared to matched controls. RESULTS: Twenty-six of 34 patients with radiologically proven RCCs had endocrine disorders. They were 9 boys and 17 girls, with ages ranging from 4.8 to 17.4 years at the time of the diagnosis. Of these, 7 (27%) had idiopathic short stature, 7 (27%) had growth hormone deficiency (GHD), and 12 (46%) had central precocious puberty (CPP). Nineteen of 26 patients (73.1%) showed low signal intensities on T1-weighted images (T1WI) and high signal intensities on T2-weighted images. The incidence of hypointensity on T1WI was higher in the patients with RCCs accompanied by endocrinopathy than in those without endocrinopathy (P=0.033). The treatment outcomes of the patients with CPP and GHD with and without RCCs were similar. CONCLUSION: CPP and GHD patients with a small RCC (less than 20 mm) expressing cystic magnetic resonance intensity can be managed with medical treatment, although the RCCs need to be closely monitored in radiological studies to observe their growth.

Intestinal Microflora and Atopy Development in Infants during the First Nine Months / 대한임상미생물학회지

BACKGROUND: The intestinal microflora varies according to the factors such as age, diet and environment. It is debated whether the changes of microbiota after birth are associated with atopic disease. The purpose of this study was to investigate colonization rates of some intestinal microflora during the initial 9 months after birth, and their association with the development of atopy. METHODS: Stool specimens were collected at 1, 3, 7 days and at 1, 2, 4, 6, 9 months after birth, and Escherichia coli, Lactobacillus, Bifidobacterium, Staphylococcus aureus were cultured with selective media. Diagnosis for atopy was accomplished via clinical history of atopy, serum total IgE, and skin prick test. RESULTS: By 12 months of age, among 48 infants, 36 (75.0%) were non-atopic while 12 (25.0%) had developed atopy. Although not statistically significant, the intestinal microflora of infants with atopy vs. non-atopy was characterized by being less often colonized with E. coli (12.5% vs. 52.4%; P=0.093) and S. aureus (0% vs. 38.1%; P=0.066) at three days after birth. Colonization rates of E. coli reached 50% after 3 days of birth in non-atopy group whereas this rate was not achieved until after 1 month in the atopy group. CONCLUSION: The intestinal colonization rates of bacteria in this study were not statistically different between atopy and non-atopy groups. Rapid colonization of E. coli and S. aureus was observed within 1 week after birth in the non-atopy group. The exact association between atopy and the bacterial colonization and/or diversity in the early days after birth has yet to be determined.

Age at menarche and adult height in girls born small for gestational age

PURPOSE: The aim of this study was to evaluate the association between birth characteristics based on birth weight for gestational age, timing of menarche and adult height in girls born small for gestational age (SGA). METHODS: Thirty subjects born from 1988 through 1999 whose birth weight below 10th percentile for their gestational ages were recruited based on hospital chart reviews. The age of each subject at menarche was recorded, and the subject's heights and bone age were assessed. RESULTS: The adult height of the girls born SGA was significantly lower than the normal adult height and slightly shorter than their target height. The adult height was associated with the birth weight for gestational age. The age at menarche was not different with the menarche timing of the general population. CONCLUSION: More attention may need to be paid to the growth outcomes of SGA patients whose birth weight is lower for their gestational age than other SGA subjects.

Age at menarche and adult height in girls born small for gestational age

PURPOSE: The aim of this study was to evaluate the association between birth characteristics based on birth weight for gestational age, timing of menarche and adult height in girls born small for gestational age (SGA). METHODS: Thirty subjects born from 1988 through 1999 whose birth weight below 10th percentile for their gestational ages were recruited based on hospital chart reviews. The age of each subject at menarche was recorded, and the subject's heights and bone age were assessed. RESULTS: The adult height of the girls born SGA was significantly lower than the normal adult height and slightly shorter than their target height. The adult height was associated with the birth weight for gestational age. The age at menarche was not different with the menarche timing of the general population. CONCLUSION: More attention may need to be paid to the growth outcomes of SGA patients whose birth weight is lower for their gestational age than other SGA subjects.

Response to three years of growth hormone therapy in girls with Turner syndrome

PURPOSE: Short stature is the most common finding in patients with Turner syndrome. Improving the final adult height in these patients is a challenge both for the patients and physicians. We investigated the clinical response of patients to growth hormone treatment for height improvement over the period of three years. METHODS: Review of medical records from 27 patients with Turner syndrome treated with recombinant human growth hormone for more than 3 years was done. Differences in the changes of height standard deviation scores according to karyotype were measured and factors influencing the height changes were analyzed. RESULTS: The response to recombinant human growth hormone was an increase in the height of the subjects to a mean value of 1.1 standard deviation for subjects with Turner syndrome at the end of the 3-year treatment. The height increment in the first year was highest. The height standard deviation score in the third year was negatively correlated with the age at the beginning of the recombinant human growth hormone treatment. Different karyotypes in subjects did not seem to affect the height changes. CONCLUSION: Early growth hormone administration in subjects with Turner syndrome is helpful to improve height response to the treatment.

Serum Alkaline Phosphatase Levels in 10-20 Year Old Healthy Korean Children and Adolescents: Based on the 2009 Korean National Health and Nutrition Examination Survey

PURPOSE: Serum alkaline phosphatase (sALP) levels show great variation with age and sex in children and adolescents. We aimed to study pediatric age- and sex-specific reference ranges for sALP and how the pattern changed according to age . METHODS: Cross-sectional results from 1366 healthy Korean children and adolescents (10-19.9 years) from the Korean National Health and Nutrition Examination Survey were analyzed. We constructed age- and sex-specific reference data for sALP with a Hitachi Automatic Analyzer 7600 using Pureauto S ALP. We assessed its peak both in relation to age. RESULTS: Reference values for sALP according to age were constructed. Peak sALP levels were found at 12-13 years in boys (P < 0.001). Total sALP levels decreased to the adult level at the age of 17 in boys and 15 in girls, respectively. CONCLUSION: This study provides reference values for sALP by age for Korean children and adolescents. This normative data that includes upper and lower limits will provide a basis from which to better evaluate sALP levels, especially for bone disorders such as rickets and vitamin D deficiency. However, caution should be made in interpreting sALP levels because different buffers might lead to different values in the same serum.

Congenital Adrenal Agenesis Presented with Adrenal Insufficiency

We report a very rare case of congenital adrenal agenesis presented with adrenal insufficiency in a 4-day-old female newborn. She was admitted with darkish skin color and seizure. Her external genitalia was normal. Elevated serum level of adrenocorticotropic hormone and increased plasma renin activity were observed. Plasma cortisol level and aldosterone level were decreased. Pelvic ultrasonography revealed bilateral agenesis of adrenal glands. Six exons of the steroidogenic factor-1 (SF-1, NR5A1) gene and their intronic flanking sequences were normal. Now, she is continuously receiving replacement doses of glucocorticoids and mineralocorticoids under adrenal insufficiency. Her growth and development are completely normal. We propose that when a patient presents with 46, XY disorder of sex development or normal female genitalia with adrenal insufficiency, SF-1 gene mutation study should be included in the differential diagnosis.

Relationship between Catch-up Growth and Changes in Insulin, Leptin, IGF-I, Adiponectin, and Ghrelin in Infants Born Full-term Small for Gestational Age / 대한소아내분비학회지

PURPOSE: The aim of the study was to investigate postnatal changes in growth and insulin, leptin, IGF-I, adiponectin, and ghrelin, and to examine the relationship of these hormones with catch-up growth in full-term small for gestational age (SGA) infants. METHODS: SGA was defined as a birth weight less than the ten percentile. Weight and height were measured at birth, 1 month, 6 months, 1 year, and 2 years of age in 70 SGA infants (40 females and 30 males). The infants were subdivided according to their weight and height catch-up growth (CUG) at 2 years old. CUG is defined as reaching a standard deviation score (SDS) of > -2 SDS. Blood samples were serially taken for insulin, leptin, insulinlike growth factor (IGF)-I, adiponectin, and ghrelin. RESULTS: 1) Dramatic CUG for weight and height occurred during the first year of life; weight and height growth gain decreased thereafter. 2) Non-catch-up growth (NCUG) infants showed more decreased weight and height growth gain than CUG infants between the first and second year of life. 3) Weight CUG was 77.1% and height CUG was 75.8% in the SGA infants. 4) Weight CUG infants showed significantly higher leptin and ghrelin levels than in weight NCUG infants at the age of 1 year (P <0.05). 5) Height CUG infants showed significantly higher leptin and ghrelin levels than in height NCUG infants at the age of 1 year (P <0.05). CONCLUSION: CUG for weight and height occurred during the first year of life and growth velocity decreased thereafter. Significant corresponding changes occurred with regard to serum leptin and ghrelin.

Insulin Resistance in Children and Adolescents Born Small for Gestational Age / 대한소아내분비학회지

PURPOSE: The aim of this study was to determine whether insulin resistance may be present and to analyze factors affecting the development of insulin resistance in children and adolescents born small for gestational age (SGA). METHODS: This study includes 24 children and 18 SGA adolescents and 13 children and 14 control adolescents. All patients underwent a standard, 2-hour oral glucose tolerance test (OGTT). Serum levels of fasting blood sugar, insulin, leptin, adiponectin, homeostasis model assessment-insulin resistance (HOMA- IR), quantitative insulin sensitivity check index (QUICKI), insulin sensitivity index (ISI), mean serum insulin (MSI) and mean serum glucose (MSG) were evaluated. RESULTS: The insulin responses at 30 min and 120 min after glucose load were significantly higher in pubertal SGA than control groups (P<0.05). Impaired glucose tolerance was found from 2 subjects (8.7 %) in prepubertal SGA group and from 3 subjects (15.0%) in pubertal SGA group. None of the patients had developed type 2 diabetes. MSI levels during OGTT were higher in pubertal SGA than in control. Pubertal SGA group had a significantly lower mean serum adiponectin level than control group (9.04+/-4.51 vs. 18.83+/-11.65 microgram/mL, P<0.05). Adiponectin level was correlated with HOMA-IR, QUICKI and ISI (r=-0.37, r=0.32, r=0.51, respectively, P<0.05). CONCLUSION: Adiponectin level was correlated with HOMA-IR, QUICKI and ISI. Pubertal SGA group had a significantly lower mean serum adiponectin level than control group. We suggest the check of insulin resistance using HOMA-IR, QUICKI, ISI and adiponectin is important for the prevention of metabolic syndrome (MS) in adolescents born SGA.

The Prevalence of Metabolic Syndrome in Children and Adolescents Born Small for Gestational Age / 대한소아내분비학회지

PURPOSE: Type 2 diabetes mellitus, dyslipidemia, hypertension, cardiovascular disease, called metabolic syndrome (MS), occur more frequently among individuals who were born small for gestational age (SGA). SGA children with catch-up growth in height and high BMI are the most insulin resistant. We investigated the prevalence of MS and evaluated the risk factors affecting the development of MS in children and adolescents born SGA. METHODS: The study population (n=65) were born less than 10th percentile in body weight for their gestational age and the body weights of the control group (n=34) were more than 10th percentile at birth. The SGA and control subjects divided into prepubertal and pubertal groups. We measured serum lipid levels (total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol), fasting sugar levels and insulin levels. Insulin resistance was determined by homeostasis model assessment, fasting insulin glucose ratio and quantitative insulin sensitivity check index. RESULTS: Systolic blood pressure was significantly higher in the pubertal SGA group than in the control group (113.2+/-0.3 vs. 98.7+/-6.4, P=0.001). The prevalence of high triglyceride and high fasting glucose levels were significantly increased in pubertal SGA group than prepubertal SGA group (P<0.05). Insulin resistance was correlated to systolic blood pressure, triglyceride levels, HDL-cholesterol levels, fasting glucose, insulin levels at fasting and 2 hours after oral glucose tolerance test and body fat mass in SGA group (P<0.05). CONCLUSION: We suggest that the monitoring of these risk factors including systolic blood pressure, triglyceride, HDL-cholesterol levels and body fat mass is important for the prevention of MS in children and adolescents born SGA.

Successful Treatment of Candida albicans Endocarditis with Liposomal Amphotericin B (AmBisome(R)) in a Very Low Birth Weight Infant

Candida albicans endocarditis is an uncommon manifestation of systemic candidiasis in newborn infants who require intensive care and develops mostly in patients with congenital heart disease; open heart surgery is the majority of predisposing factor. Improvement of techniques managing premature infants leads to increased survival rates, which give much more chances to develop fungal infections and its complications. We report a case of very low birth weight infant who had candidemia and Candida endocarditis, who was successfully treated with AmBisome(R) because of no response to conventional amphotericin B therapy.

Analyst for Windows(r), Program for Item Analysis Useful in Medical Education / 한국의학교육

This is made for teachers of medical schools not only to mark examination papers but also to do an item analysis easily. Functions of the program are marking examination result in text file, input of the result of descriptive examination, providing the result of item analysis according to the classical test theory(mean, standard deviation, reliability coefficient, answer response distribution, difficulty index, discriminating index, estimated number of examinee who select wrong answer), adding, saving and printing the results, providing, saving and printing record sheet, adding the results of equal or more than two separate examinations, sorting the record sheet by examinee's identification number and by record, input windows for item, and automatic inclusion of the result of item analysis in the item window. Much number of teachers of the medical schools may be encouraged to use this program to promote the quality of the evaluation.

The Expression of Oncogenes on the Radiation-induced Apoptosis in SCK Mammary Adenocarcinoma Cell Line / 대한방사선종양학회지

PURPOSE:The expression of p53, p21/WAF/CIP, Bcl-2, and Bax underlying the radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was investigated. MATERIALS AND METHODS: Mammary adenocarcinoma cells of A/J mice (SCK cells) in exponential growth phase were irradiated with a linear accelerator at room temperature. The cells were irradiated with 12 Gy and one hour later, the media was replaced with fresh media at a different pHs. After incubation at 37 degrees C for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Western blot analysis was used to monitor p53, p21/WAF/CIP, Bcl-2, and Bax protein levels. RESULTS:The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. The radiation-induced G2/M arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. Considerable amounts of p53 and p21 proteins already existed at pH 7.5 and increased the level of p53 and p21 significantly after 12 Gy X-irradiation. An incubation at pH 6.6 after 12 Gy X-irradiation did not change the level of p53 and p21 protein levels significantly. Bcl-2 proteins were not significantly affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis in different pHs. An exposure to 12 Gy of X-rays increased the level of Bax protein at pH 7.5 but at pH 6.6, it was slight. CONCLUSION: The molecular mechanism underlying radiation-induced apoptosis in different pH environments using SCK mammary adenocarcinoma cell line was dependent of the expression p53 and p21/WAF/CIP proteins. We may propose following hypothesis that an acidic stress augments the radiation-induced G2/M arrest, which inhibiting the irradiated cells undergo post-mitotic apoptosis. The effects of environmental acidity on anti-apoptotic and pro-apoptotic function of Bcl-2 family was unclear in SCK mammary adenocarcinoma cell line.

The Cell Cycle Dependence and Radiation-induced Apoptosis in SCK Mammary Adenocarcinoma Cell Line / 대한방사선종양학회지

PURPOSE: The relationship between environmental pH on the radiation induced-apoptosis in SCK mammary adenocarcinoma cells and cell cycle dependence was investigated. MATERIAL AND METHODS: Mammary adenocarcinoma cells of A/J mice (SCK cells) in exponential growth phase were irradiated with a 137Cs irradiator at room temperature. The cells were irradiated 1 hour after the media was replaced with fresh media at a different pHs. After incubation at 37degrees C for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. RESULTS: The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. When the cells were irradiated and maintained in pH 7.5 medium, the percentage of cells in G2/M phase rapidly increased to about 70% at 12 h after an exposure to 12Gy and returned to control level by 36 h. The percentage of cells in G1 phase decreased as the percentage of cells in G2/M increased. On the other hand, in pH 6.6 medium the percentage of cells in G2/M phases gradually increased to about 45% at 24 h after 12Gy irradiation and then slowly recessed and consequently, as much as 30-35% of the cells were still in the G2/M phase 48 h after irradiation. The percentage of cells in G1 phase then increased as the G2/M arrest began to recede. The radiation-induced G2/M arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. CONCLUSION: Radiation-induced apoptosis in SCK tumor cells are reversely suppressed in an acidic environment. Radiation-induced G2/M arrest is prolonged in an acidic environment indicating that the suppression of radiation- induced apoptosis and prolongation of radiation-induced G2/M arrest in an acidic environment are related.

The Cell Cycle Dependence and Radiation-induced Apoptosis in SCK Mammary Adenocarcinoma Cell Line / 대한방사선종양학회지

PURPOSE: The relationship between environmental pH on the radiation induced-apoptosis in SCK mammary adenocarcinoma cells and cell cycle dependence was investigated. MATERIAL AND METHODS: Mammary adenocarcinoma cells of A/J mice (SCK cells) in exponential growth phase were irradiated with a 137Cs irradiator at room temperature. The cells were irradiated 1 hour after the media was replaced with fresh media at a different pHs. After incubation at 37degrees C for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. RESULTS: The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. When the cells were irradiated and maintained in pH 7.5 medium, the percentage of cells in G2/M phase rapidly increased to about 70% at 12 h after an exposure to 12Gy and returned to control level by 36 h. The percentage of cells in G1 phase decreased as the percentage of cells in G2/M increased. On the other hand, in pH 6.6 medium the percentage of cells in G2/M phases gradually increased to about 45% at 24 h after 12Gy irradiation and then slowly recessed and consequently, as much as 30-35% of the cells were still in the G2/M phase 48 h after irradiation. The percentage of cells in G1 phase then increased as the G2/M arrest began to recede. The radiation-induced G2/M arrest in pH 6.6 medium lasted markedly longer than that in pH 7.5 medium. CONCLUSION: Radiation-induced apoptosis in SCK tumor cells are reversely suppressed in an acidic environment. Radiation-induced G2/M arrest is prolonged in an acidic environment indicating that the suppression of radiation- induced apoptosis and prolongation of radiation-induced G2/M arrest in an acidic environment are related.