Clinical course of peripheral precocious puberty in girls due to autonomous ovarian cysts.

OBJECTIVE: Peripheral precocious puberty (PPP) is the precocious development of secondary sexual characteristics without pulsatile gonadotropin-releasing hormone (GnRH) secretion. In girls, PPP suggests a hyper-oestrogenic state, such as autonomous ovarian cysts and McCune-Albright syndrome (MAS). We aimed to investigate PPP in girls with ovarian cysts, with or without MAS. DESIGN: A retrospective study design was used. PATIENTS AND MEASUREMENTS: The study included 12 girls diagnosed with ovarian cysts with PPP between January 2003 and May 2022. Pelvic sonography was performed in cases of vaginal bleeding or areolar pigmentation in PPP. The clinical characteristics, clinical course and pelvic sonographic findings of girls with ovarian cysts were investigated. RESULTS: We found 18 episodes of ovarian cysts in the 12 girls. The median size of the ovarian cysts was 27.5 mm. Five of the girls were diagnosed with MAS. The median time to spontaneous regression was 6 months. Later, 4 out of 12 girls progressed to central precocious puberty (CPP), and three of them had a recurrence of ovarian cysts. Compared to the non-recurrent and recurrent groups, there was a difference in peak luteinizing hormone (LH) in the GnRH stimulation test and period to cyst regression. CONCLUSIONS: Most ovarian cysts in PPP spontaneously disappear. However, this could be one of the findings of MAS. Some girls progress from PPP to CPP. Therefore, follow-up is necessary for ovarian cysts in patients with PPP. The recurrence of ovarian cysts may occur when spontaneous regression is prolonged.

Reference Ranges of Body Composition Using Dual-Energy X-Ray Absorptiometry and Its Relation to Tri-Ponderal Mass Index.

Introduction/background Increased body fat is related to obesity and its comorbidities later in life. To determine the amount of body fat in children and adolescents, reference intervals should be applied. Dual-energy X-ray absorptiometry (DXA) is a good tool for accurately measuring body composition. Methodology The body composition reference ranges in Korean children and adolescents were determined using nationally representative cross-sectional data. The performances of the body mass index (BMI) and tri-ponderal mass index (TMI) in measuring body fat were compared using the reference percentiles derived from this analysis. Results A total of 1,661 subjects (891 boys and men and 770 girls and women) were included. Age- and sex-specific percentiles and the corresponding LMS variables for DXA-assessed parameters for the whole body and the trunk were determined. The coefficients of determination of the whole body FM SDS and FMI SDS for the BMI SDS were 0.783 and 0.784, respectively, and those for the TMI SDS were 0.685 and 0.769, respectively. Conclusion Based on the reference values for body composition, the correlation coefficients of TMI for adjusted FM measured by DXA were comparable to those of BMI. TMI estimated body fat levels more accurately than BMI in this study population.

Aberrant Notch Signaling Pathway as a Potential Mechanism of Central Precocious Puberty.

The Notch signaling pathway is highly conserved during evolution. It has been well documented that Notch signaling regulates cell proliferation, migration, and death in the nervous, cardiac, and endocrine systems. The Notch pathway is relatively simple, but its activity is regulated by numerous complex mechanisms. Ligands bind to Notch receptors, inducing their activation and cleavage. Various post-translational processes regulate Notch signaling by affecting the synthesis, secretion, activation, and degradation of Notch pathway-related proteins. Through such post-translational regulatory processes, Notch signaling has versatile effects in many tissues, including the hypothalamus. Recently, several studies have reported that mutations in genes related to the Notch signaling pathway were found in patients with central precocious puberty (CPP). CPP is characterized by the early activation of the hypothalamus-pituitary-gonadal (HPG) axis. Although genetic factors play an important role in CPP development, few associated genetic variants have been identified. Aberrant Notch signaling may be associated with abnormal pubertal development. In this review, we discuss the current knowledge about the role of the Notch signaling pathway in puberty and consider the potential mechanisms underlying CPP.

Recombinant growth hormone therapy in children with Turner Syndrome in Korea: a phase III Randomized Trial.

BACKGROUND: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS. METHODS: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day). RESULTS: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups. CONCLUSIONS: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).

Low Bone Mineral Density at Initial Diagnosis in Children and Adolescents with Graves' Disease.

Previous studies have reported reduced bone mineral density (BMD) in patients with hyperthyroidism. We assessed the association of BMD in children and adolescents with Graves' disease (GD) after correcting for potential confounders affecting BMD such as age, sex, and pubertal status. Forty-four children and adolescents with GD and 172 age- and sex-matched healthy controls were enrolled in this study. We analyzed auxological features, BMD, and levels of thyroid hormone, thyroid-stimulating hormone, and thyroid autoantibodies. We measured BMD by dual-energy X-ray absorptiometry at the time of diagnosis in all patients. The mean age of all patients with GD (9 boys and 32 girls) was 12.1 ± 2.2 years (range, 7.0-16.0). Their initial mean free T4 and thyroid-stimulating hormone levels were 3.51 ± 1.56 ng/dL and 0.04 ± 0.03 IU/L, respectively. The mean BMD Z-scores of the lumbar spine (LS), femoral neck, and total body less head of patients with GD were significantly lower than those of control subjects. Eleven patients (26.8%) had low bone density (LS BMD Z-scores < -2.0). To identify correlations of patient characteristics with BMD Z-scores at each site, alkaline phosphatase had a significant negative correlation with BMD Z-scores at LS and femoral neck, but not total body less head (r = -0.441; p = 0.004 and r = -0.351; p = 0.025, respectively). Children and adolescents with newly diagnosed GD had lower bone mass than their healthy peers. These results suggest that BMD measurement at initial evaluation may be necessary in this population.

Impact of Type 2 Diabetes Mellitus and Antidiabetic Medications on Bone Metabolism.

PURPOSE OF REVIEW: This review focuses on the complex interactions between hyperglycemia and bone fragility and the effects of antidiabetic medications on bone metabolism. RECENT FINDINGS: Type 2 diabetes (T2D) is associated with increased risk of bone fracture even in those with increased or normal bone mineral density (BMD). The pathophysiology of diabetic bone disease is not completely understood, but it is thought to be multifactorial and associated with complex cross talk among factors such as AGEs, IGF-1, enteric hormones, and pro-inflammatory cytokines. Treatment for T2D may have an impact on bone metabolism. Diabetic bone disease should be considered a serious complication of long-standing T2D.

Identification of rare missense mutations in NOTCH2 and HERC2 associated with familial central precocious puberty via whole-exome sequencing.

Objective: Genetic factors play a critical role in pubertal progression; however, mutations associated with central precocious puberty (CPP) have been reported only in four genes: KISS1, KISS1R, DLK1, and MKRN3. This study aimed to identify novel, potentially pathogenic variants in patients with familial CPP via whole-exome sequencing (WES).Methods: WES analysis was applied in 28 patients (25 girls and three boys) belonging to 14 families, wherein all siblings were diagnosed with CPP. Data analysis aimed to select only very rare variants (minor allele frequency <1%). Nonsense, splice-site, and frameshift variants were considered the most ideal candidate variants. Additionally, non-synonymous missense variants predicted as being deleterious using in silico analysis tools were further considered.Results: The analysis of exome sequencing data resulted in the identification of rare mutations in two promising candidate genes (NOTCH2 and HERC2) in a family. Siblings with CPP exhibited two heterozygous missense mutations (p. Leu15Phe in NOTCH2 and p. Arg4081His in HERC2). Moreover, their parents without history of CPP had a missense variant in either NOTCH2 or HERC2.Conclusions: We identified new candidate genes with potential roles in pubertal development. Digenic inheritance of the two genetic mutations associated with the Notch signaling pathway may have a synergistic effect resulting in CPP.

The Relationship Between Bone Mineral Density and Type 2 Diabetes in Obese Children and Adolescents at the Time of Initial Diagnosis.

Long-term effects of type 2 diabetes mellitus (T2D) on bone health remain unclear. The objective of this study was to assess the possible association of bone mineral density (BMD) at multiple sites with T2D after correcting for several potential confounders such as age, sex, Tanner stage, and BMI known to affect BMD in adolescents with newly developed T2D. In this cross-sectional study, 17 children and adolescents with T2D and 59 age, sex, and BMI-matched controls were included. All subjects underwent dual-energy X-ray absorptiometry to measure regional and whole-body composition with Lunar Prodigy at the time of initial diagnosis. A BMD Z-score was calculated using data from healthy Korean children and adolescents after adjusting for height-for-age. The mean age of all subjects was 12.9±2.4 years (range, 8.3-18.3 years). BMDht Z-scores for lumbar spine and total body after adjusted for age, sex, BMI SDS, and Tanner stage were not significantly different between patients and controls. However, BMDht Z-scores for femur neck and bone mineral apparent density (BMAD) Z-scores of lumbar spine were significantly lower in T2D patients than those in healthy controls. HOMA-IR or HbA1c was not associated with BMDht Z-scores at multiple sites. BMDht Z-scores at multiple sites except femur neck in adolescents with newly developed T2D were similar to those in obese controls after adjustment for potential confounders.

Prevalence of Pathological Brain Lesions in Girls with Central Precocious Puberty: Possible Overestimation?

BACKGROUND: Brain magnetic resonance imaging (MRI) is routinely performed to identify brain lesions in girls with central precocious puberty (CPP). We aimed to investigate the prevalence and type of brain lesions among Korean girls with CPP and evaluate the need for routine brain MRI examinations. METHODS: This retrospective cross-sectional study evaluated data on 3,528 girls diagnosed with CPP from April 2003 to December 2016, and identified 317 girls who underwent sellar MRI. Exclusion criteria were patients with a known brain tumor or who did not undergo brain MRI due to refusal or the decision of the pediatric endocrinologist. RESULTS: Normal sellar MRI findings were observed in 291 of the 317 girls (91.8%). Incidental findings were observed in 26 girls (8.2%). None of the patients had pathological brain lesions. CONCLUSION: The prevalence of intracranial lesions among girls who were generally healthy and without neurological symptoms but diagnosed with CPP was lower than that previously reported. Furthermore, none of the identified lesions required treatment. It may be prudent to reconsider the routine use of brain MRI to screen all patients with CPP, especially if they are healthy and neurologically asymptomatic, and are girls aged 6-8 years.

No association between estrogen receptor gene polymorphisms and premature thelarche in girls.

OBJECTIVE: Premature thelarche (PT) is a benign, nonprogressive condition defined as isolated breast development. While the pathophysiology of PT remains unclear, increased sensitivity to estrogen may cause PT. The aim of this study was to investigate the association between polymorphisms in the estrogen receptor alpha (ERα) gene and PT in girls. METHODS: In this case-control study, we examined 96 girls referred for early breast development (before the age of 8 years). The control group included healthy Korean females with normal pubertal progression. Anthropometric and hormonal parameters were measured and PvuII and XbaI ERα gene polymorphisms were evaluated by PCR. Out of the 96 girls, all coding exon and exon-intron boundaries of ERα were sequenced from the DNA of 46 girls. RESULTS: There was no significant difference in the distribution of PvuII and XbaI polymorphisms between patients and controls. However, the carriers of XbaI polymorphisms had more advanced Tanner stage than did the non-carriers. Also, four ERα gene polymorphisms were previously identified, but these polymorphisms had no clinical significance. CONCLUSION: No association was found between the ERα gene polymorphisms and PT in girls. However, XbaI polymorphisms may contribute to early breast budding.

Early menarche is associated with non-alcoholic fatty liver disease in adulthood.

BACKGROUND: The aim of this study was to examine the association between early menarche (<12 years) and non-alcoholic fatty liver disease (NAFLD) in premenopausal women and to explore whether it is mediated by adult obesity and insulin resistance. METHODS: We analyzed data of premenopausal women, aged ≥15 years, from the Korea National Health and Nutrition Examination Survey (2007-2009). We divided the women into three groups: early menarche, reference (12.00-15.99 years), and late menarche. The presence of NAFLD was determined using hepatic steatosis index >36.0. RESULTS: Of the 4,387 women evaluated, 673 (15.4%) met the criteria for NAFLD. The prevalence of NAFLD was higher in both women with early and late menarche compared with the reference (early, 23.4%; reference, 14.0%; late, 19.9%, P < 0.001). After adjustment of confounders including age, the OR for NAFLD in early menarche compared with the reference was 3.04 (95%CI: 1.99-4.65). Further adjustment of mediators, such as central obesity or insulin resistance, attenuated the association to 1.91-2.17. There was no association, however, between late menarche and NAFLD after adjustment of confounders. CONCLUSIONS: Early menarche was associated with an increased risk of NAFLD in young and middle-aged premenopausal Korean women.

Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma.

Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 x 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation.

Low vitamin D levels are associated with both iron deficiency and anemia in children and adolescents.

BACKGROUND: We aimed to examine the association between vitamin D deficiency and anemia in a nationally representative sample of Korean children and adolescents. METHODS: Cross-sectional data on 2526 children and adolescents aged 10-20 years from the Korea National Health and Nutrition Examination Survey-V (2010-2012) were used. Anemia was defined according to specifications of the World Health Organization. Iron deficiency was defined as serum ferritin level of <12 ng/mL and transferrin saturation (TSAT) <16%. RESULTS: The prevalence of vitamin D deficiency in Korean children and adolescents was high especially in female (35.7% vs. 50.9%, P < 0.001). The prevalence of anemia was also higher in female (1.1% vs. 6.8%; P < 0.001). In logistic regression, risk factors for anemia were female sex, old age, post-menarche, low household income, vitamin D deficiency, and iron deficiency. The Odds Ratio for anemia, iron deficiency and iron deficiency anemia (IDA) in subjects with vitamin D deficiency (<15 ng/mL) were 1.81(95% CI, 1.13-2.88), 1.94(95% CI, 1.27-2.97), and 2.26 (95% CI, 1.20-4.24) after controlling for other risk factors. However, after examining the sexes separately, only female subjects showed statistical significance. After further controlling for iron deficiency, the risk of anemia was not significant (P = 0.261). CONCLUSIONS: Vitamin D deficiency is associated with increased risk of anemia, especially iron deficiency anemia, in healthy female children and adolescents. However, the association is attenuated after adjustment for iron deficiency. Further studies are needed to determine whether vitamin D deficiency is the cause of anemia, or bystander of nutritional deficiency which cause iron deficiency.

Association of aromatase (TTTA)n repeat polymorphisms with central precocious puberty in girls.

OBJECTIVE: Precocious puberty is characterized by early activation of the pituitary-gonadal axis. Oestrogen is the final key factor to start the onset of puberty. The cytochrome P450 19A1 (CYP19A1) gene encodes an aromatase that is responsible for the conversion of androgens to oestrogen, which is a key step in oestrogen biosynthesis. The aim of this study was to identify CYP19A1 gene mutations or polymorphisms in girls with central precocious puberty (CPP). METHODS: We evaluated the frequency of allelic variants of the CYP19A1 exons and the tetranucleotide tandem repeat (TTTA)n in intron 4 in 203 idiopathic central precocious puberty (CPP) girls and 101 normal healthy women. RESULTS: The genotype analysis of the CYP19A1 (TTTA)n polymorphism revealed six different alleles ranging from seven to 13 repeats. Among the six different repeat alleles detected in this study, the (TTTA)13 repeat allele was only detected in the patient group and carriers of the (TTTA)13 allele were significantly associated with an increased risk of CPP (OR = 1·509, 95% CI = 1·425-1·598, P = 0·033). Carriers of the (TTTA)13 repeat allele were significantly younger at pubertal onset and had higher levels of oestrogen than noncarriers of the (TTTA)13 repeat allele. Although nine polymorphisms were detected in exons of the CYP19A1 gene, no clinical significance was observed. CONCLUSION: In this study, carriers of a higher repeat (TTTA)13 polymorphism in intron 4 of the CYP19A1 gene had higher levels of oestrogen. Those carrying the (TTTA)13 repeat allele may have a higher risk of developing CPP.

Reference values for bone mineral density according to age with body size adjustment in Korean children and adolescents.

Bone acquisition failure during growth or low bone mineral density (BMD) in childhood and adolescence might increase future osteoporosis risk. To identify these children and adolescents, appropriate reference values are necessary. The robust reference values must be community based as well as sex-, age-, and ethnicity specific. In addition, body size adjustment is necessary because individuals demonstrate different body sizes and different tempos of growth, which affect measured BMD. We aimed to provide reference data with body size adjustment of Korean children and adolescents. We used dual-energy X-ray absorptiometry data of 1,650 subjects (aged 10-20 years; 788 female) from the Korea National Health and Nutrition Examination Survey (2009-2010). The BMD of each region of interest (ROI), including the lumbar spine, total body less head, total body, and femoral neck, were obtained. We calculated the mean and percentiles for each ROI. Because height and weight variations were high and correlated independently with BMD within the same age group, we developed equations to calculate the "predicted BMD Z score." Although 12.8-17.9 % of subjects with short stature showed a low measured BMD Z score depending on the measured site, only 2.6 % of those of short stature had a low adjusted BMD Z score after applying the predicted BMD Z score. We also compared the BMD of children and adolescents of other ethnicities using the same device. This study provided robust reference values for the assessment and monitoring of bone health in Korean children and adolescents. Additionally, it extended the knowledge of bone acquisition in Asian children and adolescents.

Waist-height ratio and body mass index as indicators of obesity and cardiometabolic risk in Korean children and adolescents.

PURPOSE: We assessed the clinical relevance of waist-height ratio (WHtR) as an indicator of cardiometabolic risk and body fat mass measured by dual-energy x-ray absorptiometry (DXA) among Korean children and adolescents. METHODS: Data from 1,661 children and adolescents aged 10-18 years who participated in the Korea National Health and Nutrition Examination Survey were analyzed. Unadjusted Pearson correlation, age- and sex-adjusted Pearson correlation, and multiple linear regression analyses were performed to investigate the relationships between WHtR standard deviation score (SDS) and cardiometabolic risk factors, as well as DXA-assessed parameters. RESULTS: WHtR SDS was correlated with cardiometabolic risk factors, including systolic blood pressure, glucose, total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol, as well as DXA-assessed parameters such as lean mass SDS, fat mass SDS, and fat mass percentage SDS in both whole body and trunk using an adjusted Pearson correlation analyses among all participants (p<0.001). WHtR SDS was strongly correlated with whole-body fat mass and trunk fat mass (r=0.792, p<0.001 and r=0.801, p<0.001, respectively) whereas WHtR SDS had a low correlation coefficient with whole-body lean mass and trunk lean mass SDS (r=0.512, p<0.001 and r=0.487, p<0.001, respectively). In multiple linear regression analyses, WHtR SDS was significantly associated with whole-body and trunk fat mass after adjustment for confounders. CONCLUSION: Cardiometabolic risk factors and body fat mass assessed by DXA in Korean children and adolescents were highly correlated with WHtR. Additionally, WHtR has an advantage in distinguishing fat-free mass. WHtR can be a useful and convenient clinical indicator of cardiometabolic risk factors.

Ectopic lingual thyroid with subclinical hypothyroidism in children.

OBJECTIVES: Lingual thyroid is a rare condition that affects approximately 1 in 100,000 individuals. Although it is usually detected in the pediatric population through newborn screening tests or evaluation of congenital hypothyroidism, there are cases in which it remains undetected until adulthood or until symptoms arise because of glandular enlargement. The possible symptoms of lingual thyroid include foreign body sensation in the throat, dysphagia, dyspnea, and hemorrhage. Several cases of lingual thyroid are asymptomatic and accompanied by subclinical hypothyroidism. Herein, we present three cases of lingual thyroid treated with thyroid hormone suppressive therapy. CASE PRESENTATION: The three patients sought medical attention because of a sore throat or foreign body sensation in the throat. Their newborn screening tests and developmental histories were normal. These patients exhibited subclinical hypothyroidism and were treated with hormone suppression therapy. CONCLUSIONS: Patients with lingual thyroid frequently exhibit subclinical hypothyroidism. Hormone treatment may help to reduce the size of the ectopic thyroid and improve symptoms. If an increase in size is noted during follow-up or symptoms do not improve, surgical treatments may be considered.

Impact of body mass index on luteinizing hormone secretion in gonadotropin-releasing hormone stimulation tests of boys experiencing precocious puberty.

OBJECTIVE: Excess adiposity may influence various aspects of pubertal development, including the timing of pubertal initiation and hormonal parameters during puberty. The aim of the study was to evaluate the impact of body mass index (BMI) on luteinizing hormone (LH) secretion to gonadotropin-releasing hormone (GnRH) stimulation test in boys with precocious puberty. METHODS: Boys with precocious puberty, who were normal weight, overweight, and obese underwent GnRH stimulation tests between 2003 and 2010. Subjects were classified as normal weight (BMI ≥5th percentile and BMI <85th percentile), overweight (BMI ≥85th percentile and BMI <95th percentile), and obese (BMI ≥95th percentile). RESULTS: Of 56 children whose data were included in the final analysis, mean age at diagnosis was 8.7 ± 1.0 years. The majority of boys were of normal weight (n = 28, 50%), while 15 children (26%) were overweight, and 13 (23%) obese. Peak LH levels after GnRH stimulation were 19.8 ± 8.8, 9.0 ± 3.5, and 8.1 ± 4.0 mIU/ml among normal weight, overweight, and obese subjects, respectively (p < 0.001 for all comparisons). By multivariate analysis, there was a significant negative association of BMI with peak-stimulated LH level. CONCLUSIONS: The higher BMI is associated with lower LH response to the GnRH stimulation test in boys experiencing precocious puberty. In boys with precocious puberty, BMI should be considered when interpreting GnRH stimulation test.

Healthy range of serum alanine aminotransferase and its predictive power for cardiovascular risk in children and adolescents.

BACKGROUND AND AIM: Serum alanine aminotransferase (ALT) is not only a surrogate marker of chronic liver disease but also predictive of future development of cardiovascular disease (CVD) in adults; however, pediatric reference data are rare, and "healthy-range ALT limits" have not been assessed to predict cardiovascular risk in children and adolescents. METHODS: Data from 2242 examinees (1171 boys and 1071 girls; 10-18 years of age) in the Korea National Health and Nutrition Examination Survey IV (2007-2009) were analyzed. The reference values of ALT levels were determined according to age and sex. Multiple logistic regressions were used to assess the association between healthy-range ALT limits (ALT level >30 IU/L for boys and >19 IU/L for girls) and each cardiovascular risk factor. RESULTS: The 50th, 90th, and 95th percentiles of ALT levels were respectively 14, 27, and 35 IU/L in boys and 11, 19, and 24 IU/L in girls. Subjects with ALT levels higher than healthy-range ALT limits not only exhibited higher odds ratios for metabolic syndrome but also showed higher each cardiovascular risk related to obesity, hypertension, and dyslipidemia compared with subjects whose ALT levels were within the healthy range (P < 0.001). CONCLUSIONS: The present study shows normal ALT reference data of Korean children and adolescents. The present study also showed the effectiveness of healthy-range ALT limits in predicting each cardiovascular risk factor in a national representative population.

Estrogen receptor α gene analysis in girls with central precocious puberty.

OBJECTIVE: Estrogen is the final key factor that triggers the onset of puberty. The raised sensitivity of estrogen receptor, which may be caused by an estrogen receptor α (ERα) gene mutation or polymorphism, has been implicated in the etiology of precocious puberty. The aim of this study is to identify ERα gene mutations or polymorphisms in girls with central precocious puberty (CPP). METHODS: A total of 204 Korean girls with CPP were included in this study along with 102 healthy Korean female adults as controls. All coding exons and exon-intron boundaries of the ERα gene were sequenced. The relationship between identified sequence variations and CPP were evaluated via comparison of allele frequencies between the two groups. RESULTS: Eight polymorphisms were identified in the ERα gene. Among the eight polymorphisms in this study, five have been previously reported, whereas the other three were novel polymorphisms. Two of the three novel polymorphisms, p.G145S in exon 1 and p.R555H in exon 8 were only identified in the patient group. The subgroup with p.G145S showed a significantly higher level of peak luteinizing hormone than the subgroup without p.G145S in girls with CPP. CONCLUSION: The scanning and typing of ERα polymorphism has uncovered several potentially meaningful polymorphisms. However, no solid conclusion can be made from this study and further studies are necessary to validate the function of these polymorphisms.