Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation.

Prolonged hyperinsulinemic hypoglycemia in infancy can result in developmental sequelae. A mutation in the paired box-6 gene (PAX6) has been reported to cause disorders in oculogenesis and neurogenesis. A limited number of cases of diabetes mellitus in adults with a PAX6 mutation suggest that the gene also plays a role in glucose homeostasis. The present case report describes a boy with a PAX6 mutation, born with anophthalmia, who underwent hypoglycemic seizures starting at 5 months old, and showed a prediabetic condition at 60 months. This patient provides novel evidence that connects PAX6 to glucose homeostasis and highlights that life-threatening hypoglycemia or early onset glucose intolerance may be encountered. The role of PAX6 in glucose metabolism and insulin regulation should be further investigated.

Predicting First-Year Growth in Response to Growth Hormone Treatment in Prepubertal Korean Children with Idiopathic Growth Hormone Deficiency: Analysis of Data from the LG Growth Study Database.

BACKGROUND: The first-year growth in response to growth hormone (GH) treatment seems to be the most important factor in determining the overall success of GH treatment. METHODS: Data from children (n = 345) who were in the LG Growth Study Database were used to develop a model. All subjects had been diagnosed with idiopathic growth hormone deficiency (GHD) and presented in a prepubertal state during the first year of GH treatment. RESULTS: The Δheight standard deviation score (SDS) during 1st year of GH treatment was correlated positively with weight-SDS (ß = 0.304, P < 0.001), body mass index (BMI)-SDS (ß = 0.443, P < 0.001), paternal height-SDS (ß = 0.296, P = 0.001), MPH-SDS (ß = 0.421, P < 0.001) and MPH SDS minus baseline height SDS (ß = 0.099, P < 0.001) but negatively with chronological age (ß = -0.294, P < 0.001), bone age (ß = -0.249, P < 0.001). A prediction model of 1st year growth in response to GH treatment in prepubertal Korean children with idiopathic GHD is as follows: Δheight SDS during 1st year of GH treatment = 1.06 - 0.05 × age + 0.09 × (MPH SDS minus baseline height SDS) + 0.05 × BMI SDS. This model explained 19.6% of the variability in the response, with a standard error of 0.31. CONCLUSION: The present model to predict first-year response to GH treatment might allow more tailored and personalized GH treatment in Korean prepubertal children with idiopathic GHD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01604395.

HbA1c Cutoff for Prediabetes and Diabetes Based on Oral Glucose Tolerance Test in Obese Children and Adolescents.

BACKGROUND: Oral glucose tolerance test (OGTT) is a traditional diagnostic tool for diabetes. Hemoglobin A1c (HbA1c) is an alternative method used in adults; however, its application in youths has been controversial. We evaluated the diagnostic performance of HbA1c and determined optimal cutoff points for detecting prediabetes and diabetes in youth. METHODS: This retrospective study included 389 obese children (217 boys, 55.8%) who had undergone simultaneous OGTT and HbA1c testing at six hospitals, Korea, between 2010 and 2016. Subjects were diagnosed with diabetes (fasting glucose ≥ 7.0 mmol/L; 2-hour glucose ≥ 11.1 mmol/L) or prediabetes (fasting glucose 5.6-6.9 mmol/L; 2-hour glucose 7.8-11.0 mmol/L). The diagnostic performance of HbA1c for prediabetes and diabetes was determined using the area under the receiver operating characteristic curve (AUC). RESULTS: At diagnosis, 197 (50.6%) subjects had normoglycemia, 121 (31.1%) had prediabetes, and 71 (18.3%) had diabetes. The kappa coefficient for agreement between OGTT and HbA1c was 0.464. The optimal HbA1c cutoff points were 5.8% (AUC, 0.795; a sensitivity of 64.1% and a specificity of 83.8%) for prediabetes and 6.2% (AUC, 0.972; a sensitivity of 91.5% and a specificity of 93.7%) for diabetes. When HbA1c (≥ 6.2%) and 2-hour glucose level were used to diagnose diabetes, 100% were detected. CONCLUSION: Pediatric criteria for HbA1c remain unclear, therefore, we recommend the combination of fasting and 2-hour glucose levels, in addition to HbA1c, in the diagnosis of childhood prediabetes and diabetes.

Incretin secretion in obese Korean children and adolescents with newly diagnosed type 2 diabetes.

OBJECTIVE: The role of incretins in type 2 diabetes is controversial. This study investigated the association between incretin levels in obese Korean children and adolescents newly diagnosed with type 2 diabetes. DESIGN: We performed a 2-hr oral glucose tolerance test (OGTT) in obese children and adolescents with type 2 diabetes and with normal glucose tolerance. PATIENTS: Twelve obese children and adolescents with newly diagnosed type 2 diabetes (DM group) and 12 obese age-matched subjects without type 2 diabetes (NDM group) were included. MEASUREMENTS: An OGTT was conducted and insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were measured during the OGTT. RESULTS: The mean age of the patients was 13·8 ± 2·0 years, and the mean body mass index (BMI) Z-score was 2·1 ± 0·5. The groups were comparable in age, sex, BMI Z-score and waist:hip ratio. The DM group had significantly lower homeostasis model assessment of ß and insulinogenic index values (P < 0·001). The homeostasis model assessment of insulin resistance index was not different between the two groups. Insulin and C-peptide secretions were significantly lower in the DM group than in the NDM group (P < 0·001). Total GLP-1 secretion was significantly higher in the DM group while intact GLP-1 and GIP secretion values were not significantly different between the two groups. CONCLUSION: Impaired insulin secretion might be important in the pathogenesis of type 2 diabetes in obese Korean children and adolescents, however, which may not be attributed to incretin secretion.

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

BACKGROUND: The 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). METHODS: Twenty-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. RESULTS: The 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). CONCLUSIONS: Urinary 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.

Current growth status and metabolic parameters of Korean adolescents born small for gestational age: results from the Korea National Health and Nutrition Examination Surveys (KNHANES) 2010-2011.

BACKGROUND: Currently, little information is available on current growth status and metabolic syndrome (MetS) components according to birthweight at gestational age (BWGA) on Korean adolescents. Herein, the current height and weight and MetS components of Korean adolescents who were born as small for gestational age (SGA) were compared to those of the appropriate for GA (AGA) or large for GA (LGA) groups. METHODS: Data for 2018 adolescents (aged 10-18 years) recorded in the Fifth Korean National Health and Nutrition Examination Survey 2010-2011 conducted by the Korean Ministry of Health and Welfare were assessed in this cross-sectional study. A total of 1750 subjects were assessed for current growth according to BWGA, and 792 were assessed for MetS components according to BWGA. RESULTS: From the birth history of 1750 adolescents, the prevalence of SGA, AGA, and LGA was 11.4% (n = 193), 77.7% (n = 1366), and 10.9% (n = 191), respectively. Current height-standard deviation score (SDS) and weight-SDS were significantly positively related to BWGA in all Korean adolescents (P < 0.0001). Of the 792 adolescents, the prevalence of MetS was 1.2% (n = 9). There were no differences in MetS components in Korean adolescents between SGA and AGA or LGA group. CONCLUSION: BWGA is related to current height and weight in Korean adolescents but is not related to individual components of MetS.

Causality between Sex Hormones and Bone Mineral Density in Childhood: Age- and Tanner-Stage-Matched Sex Hormone Level May Be an Early Indicator of Pediatric Bone Fragility.

This study aimed to investigate the impact of hypogonadism on bone mineral density (BMD) in children and adolescents with chronic diseases to determine the relationship between sex hormones and BMD. This retrospective study included 672 children and adolescents with chronic diseases such as hemato-oncologic, rheumatoid, gastrointestinal, and endocrinologic diseases. The relationship between the sex- and Tanner-stage-matched Z-scores for sex hormones and the sex- and age-matched lumbar spine BMD (LSBMD) Z-scores was evaluated. Adjustments were made for confounders such as underlying diseases, age at diagnosis, and age- and sex-matched body mass index Z-scores. Patients had a mean LSBMD Z-score of -0.55 ± 1.31. In the multivariate regression analysis, male testosterone showed a positive association with the LSBMD Z-score (p < 0.001), whereas female estradiol, luteinizing hormone, and follicular-stimulating hormone showed no significant association with the LSBMD Z-scores. In the male group, the testosterone level was associated with LSBMD Z-scores > -1.0 (p < 0.001), > -2.0 (p < 0.001), and > -3.0 (p = 0.002), while the estradiol level was associated with LSBMD Z-scores > -2.0 (p = 0.001) and > -3.0 (p = 0.002) in the female group. In conclusion, sex hormones are associated with BMD in children and adolescents with chronic diseases. Therefore, various measures may be necessary to predict future skeletal problems and improve bone health in these patients.

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.

Cancer and Mortality Risks of Graves' Disease in South Korea Based on National Data from 2010 to 2019.

Purpose: This study aimed to investigate Graves' disease (GD) associated cancer and mortality risk using a Korean population-based study. Patients and Methods: We included 6435 patients with GD using the Korean National Health Insurance Service-National Sample Cohort database from 2010 to 2019. Data concerning such patients were compared in a 1:5 ratio with age- and sex-matched non-GD group (n=32,175). Eighteen subdivided types of cancer and cancers-in-total were analyzed. In addition to the mortality analysis, subgroup analyses were performed according to age and sex. Results: After adjustment, the hazard ratio (HR) of the GD group for cancer-in-total was 1.07 (95% confidence interval [CI], 0.91-1.27), showing no difference when compared to the non-GD group. However, among different types of cancer, the thyroid cancer risk of the GD group was higher than that of the non-GD group (HR=1.70; 95% CI, 1.20-2.39). When subdivided by age and sex, the thyroid cancer risk of the GD group in males aged 20-39 years was higher than that of the non-GD group (HR=7.00; 95% CI, 1.48-33.12). The mortality risk of the GD group was not different from that of the non-GD group (HR=0.86; 95% CI, 0.70-1.05). Conclusion: In South Korea, patients with GD had a higher risk of thyroid cancer than the non-GD group. In particular, males aged 20-39 years with GD were more likely to have thyroid cancer than the non-GD group.

Comprehensive analysis of chemokine gene polymorphisms in Korean children with autoimmune thyroid disease.

Chemokines are chemotactic cytokines that can cause directed migration of leukocytes. The aim of this study was to examine differences in single nucleotide polymorphisms (SNP) of chemokine in AITD patients compared to normal controls. A total of 86 Korean pediatric patients were included in the patient group and 183 adults were included in the normal control group. To compare influences of several chemokine gene polymorphisms, 25 SNPs in 16 chemokine genes were analyzed. Genotype frequencies of CCL11(rs3744508)AA(OR = 6.9) and CCR2(rs1799864)AA(OR = 3.8) were higher in the AITD patients than in the controls, whereas CCL17(rs223828)CC was lower in the AITD patients than in the controls(OR = 0.4). In comparison between Graves' disease (GD) patients and controls, genotype frequency of CCL17(rs223828)CC(OR = 0.4) was lower in the GD group, whereas those of CCR2(rs1799864)AA(OR = 4.8) were higher in the GD group. The genotype frequency of CCL11(rs3744508)AA(OR = 11.3) was higher in Hashimoto's thyroiditis (HT) patients, whereas that of CXCL8(rs2227306)CC(OR = 0.4) was lower in HT patients. Polymorphisms of CCL11(rs3744508), CCL17(rs223828), and CCR2(rs1799864) might be associated with AITD, with CCL17(rs223828), CCR2(rs1799864) and CXCR2(rs2230054, rs1126579) affecting GD and CCL11(rs3744508) and CXCL8(rs2227306) affecting HT in Korean children.

The association of serum irisin with anthropometric, metabolic, and bone parameters in obese children and adolescents.

Background: Irisin is an adipomyokine secreted by muscle and adipose cells, and it plays a role in glucose, fat, and bone metabolism. This study aimed to determine the correlation of serum irisin levels with anthropometric, metabolic, and bone parameters in obese children and adolescents. Methods: This single-center study included 103 Korean children and adolescents: 54 (52.4%) obese participants with a body mass index (BMI) ≥95th percentile and 49 (47.6%) healthy controls with BMI within the 15th to 85th percentile. Various parameters were measured, including fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride and glucose (TyG) index, lipid profile, alkaline phosphatase (ALP), osteocalcin, and 25(OH)-Vitamin D levels. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry (DEXA) in 33 healthy subjects. Results: Serum irisin was significantly higher in the obese group than in the control group (mean 18.1 ± 3.5 vs. 16.2 ± 2.0 ng/mL; p = 0.001). Serum irisin level was positively correlated with chronological age (r = 0.28; p = 0.004), height SDS (r = 0.24; p = 0.02), BMI SDS (r = 0.37; p < 0. 001), fasting glucose (r = 0.27; p = 0.007), fasting insulin (r = 0.23; p = 0.03), HOMA-IR (r = 0.21; p = 0.04), osteocalcin (r = 0.27; p = 0.006) and negatively correlated with HDL cholesterol (r = -0.29; p = 0.005). All these correlations were evident in obese subjects but not in healthy subjects. ALP and 25(OH)-Vitamin D were unrelated to irisin levels. Among 33 healthy subjects, total body-less head (TBLH) BMD Z-score was positively correlated with serum irisin (r = 0.39; p = 0.03), osteocalcin (r = 0.40; p = 0.02), fasting insulin (r = 0.39; p = 0.04), and HOMA-IR (r = 0.38; p = 0.047). Conclusion: This study demonstrated an association between irisin levels and glucose, lipid, and bone parameters in children and adolescents. Our findings suggest that irisin has a potential role in metabolic disorders and bone health in obese children and adolescents.

Usefulness of glycated albumin level as a glycemic index complementing glycosylated hemoglobin in diabetic children and adolescents.

PURPOSE: Glycated albumin (GA) is a glycemic marker reflecting the average serum glucose of the previous 2 weeks. This study aimed to evaluate the usefulness of GA as a glycemic index to complement glycosylated hemoglobin (HbA1c) in children and adolescents. METHODS: Fifty-four children and adolescents with diabetes mellitus (DM) and 97 children and adolescents without DM (NDM) were enrolled. The correlation between mean blood glucose (MG) and GA compared to HbA1c was investigated in the DM group. The correlation between fasting glucose (FG) and GA compared to HbA1c was investigated in the NDM group. Factors affecting GA, HbA1c, and GA/HbA1c were analyzed. RESULTS: In the DM group, positive correlations were observed between MG and GA (P=0.003), between MG and HbA1c (P=0.001), and between GA and HbA1c (P<0.001). The correlation coefficient between MG and GA did not differ from that between MG and HbA1c in the DM group (P=0.811). Among patients with DM, those whose standardized body mass index standard deviation score (BMI SDS) was ≥2 had a lower GA/HbA1c compared with those whose BMI SDS was <2 (P=0.001). In the NDM group, there were no significant correlations between FG and GA, between FG and HbA1c, or between GA and HbA1c. The NDM subjects whose BMI SDS was ≥2 had a lower GA/HbA1c than did the NDM subjects whose BMI SDS was <2 (P=0.003). CONCLUSION: GA is comparable with HbA1c in reflecting glycemic control in children and adolescents with DM. GA is affected by obesity in children and adolescents with or without DM.

High Glycated Hemoglobin Instead of High Body Mass Index Might Increase the Urine N-Acetyl-ß-D-glucosaminidase Con-Centration in Children and Adolescents with Diabetes Mellitus.

Children with diabetes, and particularly those with obesity, have poor glycemic control. They are thus at higher risk of early microvascular complications. Renal tubulointerstitial markers are integral to evaluating diabetic nephropathy. Various biomarkers have been proposed, but their role in the obese pediatric population is uncertain. We investigated renal injury markers in children with diabetes, according to obesity, and determined their role as early predictors of diabetic nephropathy. Fifty-three children and adolescents, diagnosed with either type 1 or 2 diabetes mellitus, and 43 control children, aged 7-18 years, were included. Clinical and laboratory characteristics, including six renal injury markers, were compared among subjects according to body mass index and presence of diabetes mellitus. Urine neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and N-acetyl-ß-D-glucosaminidase (NAG) showed significant difference between controls and diabetic children, whereas urine NAG was the only biomarker that was significantly lower either in non-obese or obese controls as compared to diabetic children. Urine NGAL, KIM-1, and NAG showed significant correlations with both HbA1c and urine ACR, whereas only urine NAG was significantly correlated with HbA1c even when groups were subdivided based on the presence of either obesity or diabetes. After adjusting for age, sex, body mass index, duration of known diabetes, and urine albumin-to-creatinine ratio, HbA1c remained a significant risk factor for elevated urine NAG. Urine NAG could be a useful indicator of tubulointerstitial damage in children with diabetes in the pre-albuminuric state. Tighter glycemic control appears to be crucial for avoiding early progression to diabetic nephropathy.

Population Prevalence, Cancer Risk, and Mortality Risk of Turner Syndrome in South Korean Women Based on National Health Insurance Service Data.

PURPOSE: In South Korea, investigations into Turner syndrome (TS) prevalence and TS-associated cancer and mortality are lacking. Accurate data were estimated from the National Health Insurance Service (NHIS) and the Rare Diseases Registry (RDR) records. MATERIALS AND METHODS: Data on patients with TS who were registered in the RDR between 2007 and 2017 were collected. To estimate TS-associated cancer and mortality risk, the data were compared with data of 1:3 age-matched controls. RESULTS: In 2017, 2054 patients with TS were identified from a total population of 26186952 South Korean women; therefore, the prevalence was 7.84 per 100000 persons. TS prevalence across 10-year interval age groups were 11.82, 23.17, 18.37, 10.49, 4.09, and 0.38 for age under 10 years, teenagers, 20s, 30s, 40s, and older than 50, respectively (per 100000 persons). The cancer risk in patients with TS was higher than that of age-matched controls over 5.3 person-years [hazard ratio (HR)=1.82, 95% confidence interval (CI) 1.01-3.27, p=0.045]. Among different types of cancer, thyroid cancer risk in patients with TS was significantly higher than that of age-matched controls (HR=2.78, 95% CI 1.06-7.26, p=0.037). We also observed that TS-associated all-cause mortality risk was higher than that of age-matched controls (HR=3.36, 95% CI 1.59-7.10, p=0.002). CONCLUSION: National prevalence of TS was suggested, and an increased risk of TS-associated thyroid cancer and mortality were observed in this study.

Adrenocortical carcinoma and a sporadic MEN1 mutation in a 3-year-old girl: a case report.

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient's parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

Clinical practice guidelines for optimizing bone health in Korean children and adolescents.

The Committee on Pediatric Bone Health of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for optimizing bone health in Korean children and adolescents. These guidelines present recommendations based on the Grading of Recommendations, which includes the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines include processes of bone acquisition, definition, and evaluation of low bone mineral density (BMD), causes of osteoporosis, methods for optimizing bone health, and pharmacological treatments for enhancing BMD in children and adolescents. While these guidelines provide current evidence-based recommendations, further research is required to strengthen these guidelines.

Primary ovarian dysfunction after hematopoietic stem cell transplantation during childhood: busulfan-based conditioning is a major concern.

We evaluated the incidence of patient/treatment factors associated with primary ovarian failure (POF) after hematopoietic stem cell transplantation (HSCT) during childhood. Fifty girls over 12 years of age (15.0 +/- 2.2) who were referred to the pediatric endocrinology clinic between March 2002 and March 2010 after HSCT at the Catholic HSCT center were enrolled in the study. In total, 36 (72%) out of 50 patients developed POF. Twenty-three patients were diagnosed and treated as chronic graft-versus-host disease. As preparative regimens for HSCT, 23 patients received total body irradiation (TBI)-based regimen, 19 received busulfan (BU)-based regimen, 4 received both BU- and TBI-based, and 4 received reduced intensity conditioning regimen. In a univariate logistic regression analysis, the BU-based regimen (p = 0.028) showed a strong relationship with POF. The incidence of POF according to the route of BU administration, between orally and intravenously, were not different (p = 0.435). These results emphasize the importance of monitoring these patients at regular intervals and the need to develop complementary HSCT protocols for preventing POF in children.

Effect of Vertebral Fracture on Auxological Profiles of Children Undergoing Acute Lymphoblastic Leukemia Treatment.

Background: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and children with ALL often experience skeletal morbidity such as vertebral fractures (VF) during and after ALL treatment. Among various treatment-associated factors that affect growth pattern, the presence of VF might trigger growth impairment. Objective: This study aimed to investigate the overall VF incidence following childhood ALL treatment and examined the association of VF with growth. Methods: Children diagnosed with ALL whose treatment was completed between 2 and 15 years of age and who were screened with lateral thoracolumbar spine radiographs were enrolled. Clinical data, including anthropometric parameters were obtained at leukemia diagnosis (LD), treatment completion (TC), and 12 months following TC while VF assessment were obtained at TC and 12 months following TC. Results: In total, 155 children were included, and height status was decreased, whereas weight and BMI status were increased throughout three observational points. VF incidence at TC was 18.7%. Height status were lower in children with VF at LD, TC, and 12 months following TC, while a greater height decline was observed during the treatment period. Age and height status at LD and average glucocorticoid (GC) dose were associated VF incidence at TC. The presence of VF was a significant risk factor of height decline during the treatment period. Conclusion: A substantial number of children experienced VF following ALL treatment completion, and the presence of VF might adversely affect auxological status in children. VF detection by routine surveillance throughout childhood ALL treatment is recommended to try to prevent compromised growth.

Findings of Brain Magnetic Resonance Imaging in Girls with Central Precocious Puberty Compared with Girls with Chronic or Recurrent Headache.

In the present study, the results of brain magnetic resonance imaging (MRI) in girls with central precocious puberty (CPP) were compared those in with girls evaluated for headaches. A total of 295 girls with CPP who underwent sellar MRI were enrolled. A total of 205 age-matched girls with chronic or recurrent headaches without neurological abnormality who had brain MRI were included as controls. The positive MRI findings were categorized as incidental non-hypothalamic-pituitary (H-P), incidental H-P, or pathological. Positive MRI findings were observed in 39 girls (13.2%) with CPP; 8 (2.7%) were classified as incidental non-H-P lesions, 30 (10.2%) as incidental H-P lesions, and 1 (0.3%) as a pathological lesion (tuber cinereum hamartoma). The prevalence of positive MRI findings in girls with CPP did not differ from girls with headaches (13.2% vs. 12.2%, p = 0.74). The prevalence of incidental H-P lesions in girls with CPP <6 years of age, 6-6.9 years of age, and 7-7.9 years of age was 21.2%, 13.5%, and 9.6%, respectively (p = 0.21). Known pathological lesions were detected in only one (3.0%) girl with CPP aged <6 years and in no girls with CPP aged 6-7.9 years. Microadenomas were detected in no girls with CPP aged <6 years and in 5 (1.9%) girls with CPP aged of 6-7.9 years. Our findings call into question the routine use of brain MRI in girls with CPP, especially in girls 6 years or older. Current guidelines recommend a follow-up MRI in cases of microadenoma, but few data exist to support this recommendation for children.

Associations between Sclerostin and Anthropometric and Metabolic Parameters in Children and Adolescents.

(1) Background: Bone plays an important role in the regulation of the systemic glucose and energy metabolism. Sclerostin, secreted by osteocytes, is an inhibitor of the Wnt/ß-catenin bone metabolic pathway, and is involved in osteoporosis and metabolic disease. The aim of this study was to investigate the relationship between sclerostin and anthropometric and metabolic parameters in children and adolescents with obesity or who are overweight. (2) Methods: This study included 63 children and adolescents (20 obese, 11 overweight and 32 healthy control subjects). We evaluated the correlation between serum sclerostin and anthropometric parameters, metabolic parameters related to glucose (homeostasis model assessment of insulin resistance [HOMA-IR]), lipid, and bone metabolism (osteocalcin and 25-hydroxy vitamin D). (3) Results: Sclerostin and osteocalcin levels did not differ between obese and control groups. Sclerostin level was higher in boys than in girls (median 20.7 vs. 18.9 pmol/L, respectively; p = 0.04). In all subjects, sclerostin levels were negatively correlated with fasting insulin (r = -0.26; p = 0.04) and HOMA-IR (r = -0.28; p = 0.03), and positively correlated with serum concentrations of triglycerides (r = 0.29; p = 0.04), alkaline phosphatase (r = 0.41; p = 0.002), and osteocalcin (r = 0.33; p = 0.008). In obese patients, sclerostin levels were correlated negatively with fasting glucose (r = -0.49; p = 0.03) and HOMA-IR (r = -0.48; p = 0.03) and positively correlated with triglyceride levels (r = 0.53; p = 0.02). In the healthy control, sclerostin levels were correlated negatively with fasting insulin levels (r = -0.61; p < 0.001) and HOMA-IR (r = -0.36; p = 0.04). After adjusting for age, sex, and height SDS, a negative correlation between sclerostin and HOMA-IR was found (r = -0.39; p = 0.003) in all of the subjects. This association was more evident in obese patients (r = -0.60; p = 0.01) than in healthy controls (r = -0.39; p = 0.047). (4) Conclusions: Among children and adolescents with obesity, serum sclerostin was negatively correlated with HOMA-IR. Further studies are needed to clarify the mechanisms involved to understand how sclerostin affects the glucose metabolism.