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 summarize the experience in diagnosis and treatment of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism and bilateral gonadoblastoma (Gb) secreting human chorionic gonadotrophin(HCG). Methods: A female patient aged 5 years and 3 months was admitted to the hospital with a complaint of "enlarged breasts for 27 months, and elevated blood β-HCG for 8 months". The clinical data were summarized, and related literature up to March 2022 with the key words"Turner syndrome" "Gonadoblastoma" "Y chromosome" "human chorionic gonadotropin" "precocious" in PubMed, CNKI and Wanfang databases were reviewed. Results: The girl went to the local hospital for 2-month breast development at age of 3 years, and was found with a heart murmur diagnosed with "pulmonary venous malformation and atrial septal defect (secondary foramen type)". Surgical correction was performed. She experienced the progressive breast development, rapid linear growth and markedly advanced skeletal age, which cannot be explained by partial activation in the hypothalamic-pituitary-gonadal axis determined at the age of 3 years and 7 months in local hospital. Then whole-exome sequencing revealed chromosome number abnormality 45, X, which was confirmed by Karyotyping. At the age of 4 years and 6 months, serum β-HCG was found to be elevated (24.9 U/L) with no lesion found at the local hospital. On physical examination, she was found with breast development, pubic hair development and clitoromegaly with elevated serum testosterone (1.96 μg/L) and β-HCG (32.3 U/L). Sex determining region Y(SRY) gene was negative in peripheral blood sample. Thoracic and abdominal CT, head and pelvic magnetic resonance imaging were normal. Exploratory laparotomy confirmed the presence of a left adnexal tumor and a right fibrous streak gonad. During surgery, simultaneous samples of bilateral gonadal and peripheral venous blood were obtained and serum β-HCG, estradiol and testosteron concentrations was higher to lower from left gonadal venous blood, right gonadal venous blood, to peripheral venous blood. Bilateral gonadectomy was performed. Histopathology revealed bilateral gonadoblastomas. SRY was positive in bilateral gonadal tissues. After surgery, serum E₂, testerone and β-HCG returned to normal. So far 4 cases of HCG-secreting gonadoblastoma had been reported worldwide. The phenotypes of the 4 cases were all female, with virilization or amenorrhea, and the preoperative peripheral blood β-HCG concentrations were 74.4, 5.0, 40 456.0, and 42.4 U/L, respectively. Conclusions: There is a high risk of Gb in TS with Y chromosome components. Gb is infrequently presented with breast development, and Gb associated with HCG secretion is rare. Karyotyping should be performed in a phenotypic female with masculinization, and virilization in TS indicates the presence of Y chromosome material with concurrent androgen secreting tumors.
Humans ; Female ; Child, Preschool ; Gonadoblastoma/surgery* ; Turner Syndrome/complications* ; Virilism ; Chorionic Gonadotropin ; Ovarian Neoplasms

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 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.

[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.

Objective To explore the application of furosemide/hydrochlorothiazide load test in clinical classification of Bartter syndrome and Gitelman syndrome and the significance of selecting target genes. Method The clinical features, biomarkers, the furosemide/hydrochlorothiazide load test, and gene detection in 5 patients with Bartter syndrome and Gitelman syndrome were retrospectively analyzed during 2012 to 2014. Results All of those 5 patients were manifested low potassium and metabolic acidosis; basis of renin, angiotensin II, and aldosterone were elevated. The blood pressures were normal. Most of the patients suffered from polydipsia, diuresis, and different degrees of growth retardation. The gene analysis of these 5 patients made the same diagnoses as furosemide/hydrochlorothiazide load test did. Conclusions Furosemide/hydrochlorothiazide load test can make a differentiation of Bartter syndrome from Gitelman syndrome and thus it can guide the selection of targeted gene detection.

Objective To compare the different efficacies of recombinant human growth hormone (rhGH) alone and rhGH combined with low-does stanozolol on growth velocity (GV) of girls with Turner syndrome (TS). Methods 51 girls with TS were divided into two groups: Group 1 (n = 23) were treated with rhGH alone and group 2 (n = 28) with rhGH combined with low-does stanozolol both for more than six months. The two groups were compared in terms of GV, height standard deviation score for chronologic age (HtSDSCA), HtSDS for bone age (HtSDSBA), HtSDS (ΔHtSDS) and the ratio of ΔBA/ΔCA. Results In the first year, the GV was (6.29 ± 1.44) and (8.13 ± 1.87) cm/a in Group 1 and Group 2, respectively. HtSDSCA changed from (-3.51 ± 0.99) to (-3.19 ± 1.09) and (-4.21 ± 1.19) to (-3.43 ± 1.06), and ΔBA/ΔCA was (0.60 ± 0.39) and (0.77 ± 0.56) in Group 1 and Group 2, respectively. The GV and ΔHtSDS in Group 2 were significantly better than Group 1 (P < 0.05). The GV was negatively correlated with the age. Conclusion Compared with the therapy with rhGH alone, the one with rhGH combined with low-dose stanazolol is more effective in improving GV without accelerating bone maturation among the girls with Turner syndrome.

Objective To summarize the characterization of ovarian adrenal rest tumors (OART) in children and adolescent females with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD).Method We have diagnosed 4 cases of CAH 21-OHD with OART in the recent 5 years in pediatric endocrinology unit of the first affiliated hospital of Sun Yat-Sen University.Clinical characterizations were summarized,including symptoms,growth patterns and bone age advancements,serum steroid concentrations,imaging results and the follow-up data.Result The 4 cases of OART accounted for 2.5 ％ of the CAH 21-OHD girls,which was much lower than the detection rate,29.5％,of testicular ART in our patient group during the same period.The 4 cases included 3 salt wasters and 1 with simple virilizm.OART were diagnosed at the age of 8.9 years,15.8 years,21.4 years and 9.3 years,respectively.Before the diagnosis of OART,their daily hydrocortisone doses reached 16 mg/(m2 · d)to 24 mg/(m2 · d).The patients presented with deteriorated acne,deepened voice,amenorrhea (2 cases),accelerated growth and advanced bone age,△BA/△CA reached 1.2 (during GnRHa treatment) and 2.0.Their serum adrenal steroids increased significantly and hyperplasia of adrenal glands were found in all patients.The diagnosis could be confirmed before the operation in only 1 case.The diagnosis could not be made until the planned sub-total adrenalectomy in the other 3 cases.The follow-up periods of OART were 4.8,4.7,3.8and 2.7years,respectively.Removal of OART resulted in symptoms relief at least partialy and lowered daily hydrocortisone doses,14 to 19 mg/(m2 · d).Conclusion The detection rate of OART was much lower than testicular ART.Before the diagnosis of OART,the patients presented with deteriorated virilescence,accelerated growth and advanced bone age,elevated serum adrenal steroids and hyperplasia of adrenal glands.Removal of the OART resulted in symptoms relief at least partialy.

Objective To explore the possible role of NROB1 gene played in regulating hypothalamic-pituitary-gonad axis(HPGA) by analyzing the clinical and molecular characteristics in a case of central precocious puberty(CPP) with NROB1 gene mutation. Methods Clinical characteristics and direct sequencing of NROB1 gene in the patient were analyzed. Results A 11-month-old boy with manifested premature puberty, enlargement of penis/testes, and penile erection, but without manifestations of adrenal insufficiency was reportd. Clinical diagnosis was adrenal hypoplasia congenita( AHC) with CPP. The NR0B1 gene sequencing revealed a novel mutation in exon 1 (913C> T). Conclusion NR0B1 gene mutation may lead to the development of CPP in the patient with AHC. However, the mechanism remains unclear and thus deserves further exploration.