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.

〔Abstract〕 The paper overviews the development status of physical examination system, designs and constructs C/S based distributed students physical examination system, introduces design priciples, system architecture and main function models.The design and development of this system could resolve the data sharing problem among the students and their parents, schools and hospitals, it has practical significance.

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 summarize the prevalence,risk factors,and characteristics of testicular adrenal rest tumors(TART) in children and adolescent males with congenital adrenal hyperplasia(CAH) due to 21-hydroxylase deficiency (21-OHD).Methods During past 4 years,there were 44 males with CAH caused by 21-OHD undergone testicular ultrasound scan in our clinic.We have diagnosed 13 cases of TART and summarized the characterizations.Results The prevalence of TART in our group was 29.5％ with 11 cases of salt wasters and 2 cases of simple virilizers.The median age of TART diagnosis was 10.2 years.The median follow-up period of TART was 3.0 years.History of poor control of CAH was found in every case before diagnosis of TART.The doses of hydrocortisone were increased in 5 cases of TART who refused operations or had small TART,resulting in tumor regression in two of those five patients.Testis-sparing surgeries were performed in 8 patients with symptoms relieved; 7 of those eight patients presented elevated FSH and LH after operations.Conclusions Prevalence of TART in our CAH children and adolescent males was 29.5％.Testicular ultrasound was useful in TART screening.TART should be considered when a CAH patient with poor control,especially in post-pubertal one.Delayed management of TART may lead to impaired testicular function.Increased doses of glucocorticoid may be effective in TART of small size.Testis-sparing surgery should be also considered if necessary.

Forty girls with Turner's syndrome (TS),aged (12.6 ± 1.9) years,were treated with daily subcutaneous injection of recombinant human growth hormone (rhGH,1.0 ～ 1.1 IU · kg-1 · w-1) and oral stanozolol (0.02 ～ 0.04 mg · kg-1 · d-1) for 1 ～ 5 years.Growth velocity (GV),height standard deviation score (SDS) by reference of healthy Chinese girls (HtSDSNor) and height SDS by reference of untreated Chinese TS girls (HtSDSTs)were evaluated regularly.Of the forty girls studied,thirteen had discontinued the treatment after a mean duration of (2.9 ± 1.2)years when GV was less than 2 cm/year or when patients were satisfied with the achieved height.Final adult height (FAH) or near-final height,which was defined as the most recent available height after discontinuation of treatment,and the height gained in the thirteen girls were evaluated.Estrogen therapy was started at the age of(16.0 ± 1.1) years.HtSDSNor increased from-4.2 ± 1.0 to-3.4 ± 1.0 in the first year,and-2.8 ± 1.0,-2.4 ± 0.8,-2.5 ± 0.5,-2.3 ±0.3 respectively in the 2nd,3rd,4th,and 5th year.The change in HtSDSTs was similar to HtSDSNor.It was increased from 0.1 ± 0.9 to 1.0 ± 0.9 in the first year,and to 1.5 ± 0.8,1.9 ± 0.6,1.7 ± 0.4,1.7 ± 0.2 in the subsequent 4 years.The predicted adult height (PAH) in 13 girls was (142.8 ± 4.2) cm before treatment.FAH was (151.7 ± 4.1) cm,which was significantly higher than PAH (P＜0.01),and the mean height gain was (8.9 ± 2.8) cm (5.1 ～ 12 cm).FAHSDSNor was increased to-1.6 ± 0.8 from-3.8 ± 0.8.For girls with TS around 9 years of age,combined therapy with rhGH and low dosage of stanazolol may significantly increase growth velocity and improve final adult height.

[ ABSTRACT] AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue ( GnRHa) and growth hormone ( GH) on the linear growth in mid-and late pubertal girls at great bone ages with central precocious puberty ( CPP) or early and fast puberty ( EFP) , and to determine the relation between C-type natriuretic pep-tide ( CNP) signaling pathway and the accelerative effect of GH on long bone growth in these girls.METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height ( PAH) , and divided into GnRHa treatment group ( treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group ( treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc) .The height, weight and pubertal stage were determined every 3 months.At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide ( NT-proCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity ( HV) , height SD score for bone age ( HtSDSBA ) , PAH and the serum indexes mentioned above were com-pared at the beginning and the end of the treatment.RESULTS: After 6 months of the treatment, HV, ΔHtSDSBA andΔPAH of the girls treated with GnRHa +GH were statistically higher than those of the girls given GnRHa alone ( P <0.01).Serum concentrations of NTproCNP, P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment.The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION:In the CPP or EFP girls who are in mid-and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height.This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.

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 assess the effect of early menarche and treatment with gonadotropin-releasing hormone analogs ( GnRHa ) in girls with central precocious puberty ( CPP ) or early and fast puberty ( EFP ) on menstrual regularity. Methods Six hundred and ten healthy girls were recruited and their menarche age and menstrual cycle were recorded. 169 CPP or EFP girls treated with GnRHa were followed up, and their menarche age and menstrual cycle were also recorded. Results There were 129 girls with irregular menstruation among 610 healthy girls(21. 1%), with 10 in 44 early menarche girls(22. 7%) and 11 in 44 late menarche girls(25. 0%). Compared with normal menarche girls(17. 2%), no significant difference was found in the incidences of irregular menstruation in early and late menarche girls. The incidences of dysmenorrhea were 41. 1% in normal girls and 50. 0% in early menarche girls, without significant difference. There was a higher incidence of irregular menstruation in 113 CPP girls and 56 EFP girls treated with GnRHa compared with healthy girls (31. 4% vs 21. 1%, P<0. 05), but without difference compared with early menarche girls(P>0. 05). Fifty-seven cases treated with GnRHa(33. 7%) suffered from dysmenorrhea, and there was no significant difference as compared with healthy girls and girls with early menarche. Conclusion The incidence of irregular menstruation was similar in early menarche girls and normal girls. CPP and EFP girls with GnRHa treatment had a significantly higher incidence of irregular menstruation than normal girls, but no difference was found as compared with girls with early menarche. Early menarche and GnRHa treatment did not affect the incidence of dysmenorrhea.

[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.