ObjectiveTo explore the effect of precocious puberty on glucose metabolism and lipid metabolism in female rats. MethodsSixty two-day-old female rats were randomly divided into 2 groups. When aged 5 days， the precocious puberty group and normal group were given a single subcutaneous injection of danazol and solvent soybean oil respectively. The vaginal opening of rats was monitored from their 21 days of age. After 12 hours of fasting， all successful modeling rats were randomly executed within 3 days after vaginal opening， when aged 7 and 12 weeks. Then we measured the rats’ body weight and length， determined the concentrations of glucose， insulin， blood lipids， estradiol， leptin and adiponectin with enzyme-linked immunosorbent assay and observed the pathological changes of perirenal fat， uterus and ovary. ResultsFor body weight and length， rats in the precocious puberty group were smaller than those in the normal group within 3 days after vaginal opening， but which did not affect their subsequent growth and development， and there was no significant difference between the two groups at 7 and 12 weeks of age. Within 3 days after vaginal opening， insulin levels had significant difference between the two groups （P = 0.001）， the precocious group showed hyperinsulinemia and increased number of perirenal adipocytes. At three execution times， no significant difference was noted in estradiol， leptin and adiponectin levels between the two groups. The same was true in the ratios of ovary or uterus to body weight between the two groups. ConclusionsPrecocious puberty makes earlier onset of pubertal development and allows body maladaptation to the sudden changes of the internal environment. However， the changes due to precocious puberty are temporary and reversible， and they may become normal in adulthood.

[Objective]To present a case of complete androgen insensitivity syndrome (CAIS) coexisting with Müllerian duct remnants (MDR) and to review previous reports in the literature to enhance the understanding of the clinical manifestations and pathophysiology of CAIS.[Methods]The study aimed to diagnose complete androgen insensitivity syndrome (CAIS) by conducting physical examinations,chromosomal analysis,whole exome sequencing,laboratory tests including follicle-stimulating hormone (FSH),luteinizing hormone (LH),total testosterone,estradiol,anti-Müllerian hormone (AMH),inhibin B,dehydroepiandrosterone sulfate (DHEAS),androstenedione,17-hydroxyprogesterone,and imaging studies such as pelvic ultrasound and pelvic magnetic resonance imaging (MRI). Laparoscopy revealed the presence of Müllerian duct structures. Additionally,the study reviewed similar cases of CAIS combined with Müllerian duct remnants reported in the literature.[Results]The child presented with female phenotype,elevated levels of FSH,LH,and testosterone. Pelvic MRI showed bilateral cryptorchidism without visible uterus or fallopian tubes. The chromosomal karyotype was 46,XY,and whole exome sequencing identified a pathogenic variant in the androgen receptor (AR) gene,c.2359C>T (p.Arg787*). No abnormalities were found in the AMH and AMHR2 gene tests. Laparoscopic exploration revealed underdeveloped testes and an underdeveloped uterus. Pathology showed the presence of fallopian tube-like structures next to the testicles. A total of 11 cases with genetically confirmed diagnosis of CAIS coexisting with MDR were retrieved from the database. The findings suggest that the initial clinical presentation,biochemical data,and gonadal pathology of CAIS with MDR are similar to those without MDR.[Conclusion]The study reports a patient with CAIS coexisting with MDR,which broadens the clinical spectrum of CAIS and provides a perspective for basic research on Müllerian duct regression that is independent of the AMH-AMHR2 signaling pathway.

Objective:To summarize the clinical and genetic features of 7 patients with a mild form of Geleophysic dysplasia type 2(GD2)/Acromicric dysplasia(AD) induced by fibrillin 1(FBN1) gene mutation from one Chinese family.Methods:A Chinese pedigree of mild GD2/AD treated at the Pediatric Endocrinology Department at the First Affiliated Hospital of Sun Yat-sen University between August 2017 and May 2022 was collected. Whole-exome genetic sequencing of the FBN1 gene were performed to establish the diagnosis. Additionally, a literature review was further conducted.Results:In this family, among 13 individuals spanning three generations, there were 7 affected cases, including 1 adult female, 1 adult male, and 5 children. All individuals exhibited postnatal growth failure, severe disproportionate short stature, and lacked typical facial features. Exome sequencing and Sanger sequencing confirmed the presence of a heterozygous missense mutation c. 5099A>G(p.Tyr1700Cys) in exon 42 of the FBNI gene in 6 affected individuals(Ⅱ-1, Ⅲ-1 to Ⅲ-5), which was identified as a pathogenic mutation. This mutation was previously reported in a Chinese classical achondroplasia(AD) family. Based on comprehensive genetic analysis, clinical features, and multisystem evaluation, 3 cases were diagnosed with mild type 2 growth hormone deficiency(GD2), and 4 cases were diagnosed with mild AD. Recombinant human growth hormone(rhGH; 1.1-1.4 IU·kg -1·week -1) was applied to all the 5 children, and additional gonadotropin releasing hormone analogue(GnRHa) was administered to the 2 girls in late puberty, resulting in certain growth-promoting effect. Conclusions:The c. 5099A>G(p.Tyr1700Cys) mutation not only leads to the classical type of achondroplasia(AD) as reported in the literature but also causes the non-classical GD2 or AD(mild GD2/AD). Further research is warranted to investigate the long-term therapeutic effects of rhGH treatment.

OBJECTIVE: To explore the cause for the failure of non-invasive prenatal testing (NIPT) and feasibility of repeated testing. METHODS: Clinical data, test results and pregnancy outcomes of 40 311 pregnant women who received NIPT test from January 2011 to December 2018 were reviewed. RESULTS: Among all the pregnant women, 1116 cases failed in the first test, 9 cases (0.81%) had fetal free DNA concentration lower than 4%, 663 cases (59.41%) were retested after the establishment of Z value gray area, and the remainder 444 cases (39.78%) needed to be retested after the blood collection due to the fetal free DNA concentration lower than 4%. After retesting, 1069 cases (95.78%) obtained effective NIPT results. The results showed that 53 cases were at high risk (6 cases for trisomy 21, 6 cases for trisomy 18, 13 cases for trisomy 13, 16 cases for sex chromosomal abnormality, 12 cases for chromosomal copy number variation). Forty-eight cases were selected for invasive prenatal diagnosis, and 2 cases of 47, XXY and 2 CNV were confirmed. A total of 47 cases (0.12%) did not obtain results because the concentration of fetal free DNA was lower than 4%. Only 16 cases (34%) chose invasive prenatal diagnosis. CONCLUSION Repeated detection of the gray area of Z value can reduce the false positive rate of NIPT and invasive prenatal diagnosis, and the feasibility of repeated detection is high. In the case of fetal free DNA concentration lower than 4%, the success rate of obtaining effective NIPT results by re-sampling and re-detection increases with the increase of gestational age, but may delay the diagnosis for fetal aneuploidies. Therefore, personalized estimation should be made according to gestational age and clinical indications. It is suggested that pregnant women should choose invasive prenatal diagnosis when they have failed in the retest.

To evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). Seventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. HV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( < 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( =2.78 and 2.20, all < 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( >0.05), and both were higher than that in no intervention group (162±4 cm, < 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. Long term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.
Adolescent ; Body Height ; Bone Development ; Child ; Gonadotropin-Releasing Hormone ; Growth Disorders ; Humans ; Letrozole ; therapeutic use ; Male

Objective: To explore the nursing experience of growth hormone provocative test in pediatric clinic. Methods: Five thousand and thirty-six children with short stature or slowing growth received combined simultaneous Levodopa Pyridostigmine stimulation test from June 2008 to October 2018 in the Child Growth Center of the First Affiliated Hospital of SUN Yat-sen University. Comprehensive nursing intervention was conducted to ensure the test carry through successfully before, during and after the test. Results: All children completed the five collections in the 120-minute growth hormone provocative test without cannula obstruction and blurt out. Some (986 out of 5 036 children, 19.58%) had different degrees of adverse reactions including nausea, vomiting, abdominal pain, sweating, salivation, dizziness, pallor, etc., most of which disappeared or alleviated after nursing, except 11 patients (0.22%) needed atropine muscular injection and 3 of whom needed intravenous fluids to release the marked symptoms. Conclusion Combined simultaneous Levodopa Pyridostigmine stimulation test is safe and practicable in pediatric clinics with nursing experience.

Objective To explore the risk factors for orchidism and the curative efficacy of intensive corticosteroids therapy for the testicular adrenal rest tumors ( TART ) in the patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency ( 21OHD) during childhood and pubescent periods. Methods A total 12 cases (27 case-times) with TART were adopted in intensive corticosteroids therapy, 7 cases (7case-times) as control group without intensive therapy. Retrospective analysis following parameters:( 1) The testicular volume and the echogenic characteristics of TART by B-mode ultrasound. ( 2 ) Serum levels of FSH, LH, testosterone, 17-hydroxyprogesterone, androstendion, and inhibin-B were measured. ( 3 ) Orchidism was defined by one of following events:serum level of inhibin-B≤3rd％ for norm, and/or serum level of testosterone<1. 47 ng/ml for the individual which is already in TannerⅣstage. ( 4) The relationship between regression of TART and intensive therapy project. Results The prevalence of TART in 21-OHD was 28.18％during 2-18 years old, and the youngest age with TART was 2. 48 year of old. The regression rate of TART by intensive therapy was higher than that of the control significantly, 20/30 and 1/11(tumor-times) respectively(P=0.004). When the dose of dexamethasone≥30％ of total doses of corticosteroids, the regression rate of TART was higher than those less than 30％ ones, or adopted hydrocortisone alone, were both respectively 16/20 and 4/10(P=0.045). The risk factors for orchidism related to early diagnosis:The TARTs stages in diagnosis (≥stages III;P=0.003) , the tumor in size, hyperechogenicity in B ultrasound of the tumors ( P = 0. 003 ) . Inhibin-B is the earliest displayed biochemical warker for orchidism. Conclusions The TART could regress when got early diagnosis and adopted intensive corticosteroids therapy on time. Delayed diagnosis was the main risk factor for orchidism. For early diagnosis of TART, we suggest to conduct the scrotal ultrasound regularly started from 2 years of age.

46,XX primary ovarian insufficiency(POI)is a clinical syndrome defined by loss of ovarian activity before the age of 40 years old with a karyotype 46,XX,characterized by menstrual disturbance(amenorrhea or oligomenorrhea)in association with hypergonadotropic hypogonadism.46,XX POI is a rare disease with the prevalence lower than 1％,of whom 2.5％are adolescents.Potential etiologies for 46,XX POI can be divided into genetic,autoimmune,and iatrogenic categories.Unfortunately,for most patients presenting with POI,the cause will remain unexplained.Once,POI is diagnosed,clinical indicated tests are needed to identify the mechanism causing POI.POI is a complex condition appearing with a strong genetic basis.Large-scale genomic sequencing had recently identified new mechanisms of POI.The management of the condition should address both of physical and emotional well-being health,including health education,hormone develoment treatment,prevention and treament of lower-estrogen associated diseases,with the support from a multidisciplinary team.

[Objective] To observe the efficacy of metformin treatment on non-alcoholic fatty liver disease (NAFLD) in obese children.[Methods] A retrospective analysis was performed of 10 patients over 10 years old with NAFLD from July 10,2013 to August 23,2016.These patients were treated with metformin in pediatric endocrinology outpatient department of the First Affiliated Hospital of Sun Yat-sen University.The changes of liver ultrasonography,hepatic enzymes,blood lipids,blood glucose,insulin,HOMA-IR,BMI,and waist circumference height ratio were compared before and after treatment with metformin.[Results] There were 10 cases of NASH,including 5 boys and 5 girls.The short-term treatment of metformin reduced the levels of ALT,AST,and HOMA-IR for all 10 patients (P ＜ 0.01).ALT,gradually decreased with the course of treatment.Fasting insulin and waist circumference to height ratio also improved with the treatment (P ＜ 0.05);the changes of TG,BMI,and fast glucose were not obvious (P ＞ 0.05).[Conclusion] Metformin can effectively reduce liver enzymes and improve insulin sensitivity in children with NASH in short term,the improvement of TG and BMI in short term is not obvious.

[Objective] We assessed in a retrospective unicenter study the state of metabolism and gonadal axis of early menarche girls and girls who treated with Gonadotropin-releasing hormone analogs (GnRHa).[Methods] Thirty-nine early menarche girls and 58 girls who had been treated with GnRHa were enrolled in our study and 19 normal menarche girls were enrolled as control group.Data were collected in height,weight,gonadal hormone,blood glucose,insulin,blood lipid,leptin,adiponectin and the size of uterus and ovary.[Results] Both BMI SDS for chronological age (CA) and for bone age (BA) of early menarche girls were significantly higher than normal menarche girls (P ＜ 0.05).The ratio of insulin resistance in early menarche girls (20.5％) was also significantly higher than normal girls (0％).No significant difference in lipid metabolism and gonadal axis between two groups.In girls treated with GnRHa,BMISDS,insulin,HOMA-IR and the ratio of insulin resistance (20.7％) were all significantly higher than normal group (P ＜ 0.05).Meanwhile,DHEAS,androstenedione and testosterone of GnRHa treated girls were significantly higher than early menache girls,and DHEAS was higher than normal girls.The size of uterus in treated group was larger than the other two groups.[Conclusion] Early menarche and GnRHa treatment may take negative effect to BMI and glucose metabolism.Androgen was higher in GnRHa treated group.Therefore,suggestion was that BMI,insulin,blood glucose and androgen should be monitored in early menarche girls and girls treated with GnRHa.