Objective To observe the final adult height of 20 boys with idiopathic central precocious puberty (ICPP) treated with slow-releasing gonadotropin-releasing hormone analogue(GnRHa).Methods Twenty boys with ICPP were treated with GnRHa for( 20.0 ± 6.1 ) months.At the beginning of therapy,mean chronological age and bone age was( 11.4 ± 1.0 ) years and ( 13.0 ± 0.4 ) years,respectively,GnRHa was discontinued when the boys reached the chronological age and bone age of( 13.2 ± 1.1 ) years and ( 13.7 ± 0.6 ) years,respectively.After the end of treatment,all the boys had been followed up for( 3.3 ± 1.5 ) years and had achieved adult height.Comparisons were made among their predicted adult height ( PAH ),final adult height ( FAH ),and target height ( THt ).The long-term outcome of final adult height in boys with ICPP was investigated after GnRHa treatment.Results All the boys reached target height range.Final height was similar to the target height [ ( 169.8 ± 5.8 vs 167.8 ± 4.6 ) cm,P＞0.05 ].The height gain,defined as the difference between predicted adult height at the start of treatment using the height SDS for bone age and actual adult height was( 3.62 ± 3.57 ) cm with the residual growth capacity of ( 11.82 ±3.99)cm,PAH significantly improved after GnRHa treatment compared with before treatment [ ( 169.0 ± 5.0 vs166.2 ± 4.2 ) cm,P＜0.01 ].There were no differences among PAH,FAH,and THt.Conclusion GnRHa treatment improves final height within the range of target height in boys with central precocious puberty.

Objective To analyze the clinical characters of childhood adrenocortical tumors, and to enhance the knowledge of diagnosis of this disease. Methods A retrospective analysis of clinical characters,laboratory tests,and imaging findings in 31 cases of childhood adrenocortical tumors was carried out. Results 16 cases of adenoma and 15 cases of carcinoma were included. The average age was (4.49±3.51) years old, and 67.7% of the patients were younger than 5 years old. The ratio of male to female was 1.0: 1.4. 12 patients presented only precocious sexual development, 4 patients presented only Cushing syndrome, 10 patients showed sexual precocity combined with Cushing syndrome, and 5 patients did not have any endocrine abnormalities. Raised testosterone level in 92.3% of these patients was the most common finding in laboratory tests. Only 12.5% of ultrasound images and 20.8% of CT images were consistent with pathologic diagnosis. Conclusions The clinical manifestations of adrenocortical tumors in childhood are precocious sexual development, Cushing's syndrome, or nonfunctional. The common laboratory findings are elevation of sex hormone and disorder of cortisol circadian rhythm. Precocious sexual development and elevation of androgens are more common in childhood adrenocortical tumor than those in adults. Imaging usually cannot give proper diagnosis. Final diagnosis should be established by clinical features, laboratory tests, imaging, and pathologic results.

[ 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 assess the efficacy and impact factors of treatment with Gonadotropin-releasing hormone analogs (GnRHa) in central precocious puberty (CPP) or early and fast puberty (EFP) girls in a retrospective unicenter study.Methods One hundred and two girls (75 CPP and 27 EFP) were treated with GnRHa alone and were followed up to their final adult hight (FAH).Results FAH was (158.0 ± 4.8) cm,being significantly higher than pretreatment predicted adult height [(151.1 ±5.1) cm,P＜0.01].There was no significant difference between CPP [(7.3 ± 4.4) cm] and EFP [(5.5 ± 4.5) cm] in net height gain.There was no significant improvement in FAH and pretreatment PAH for the patients who had menarche before treatment or whose growth velocity was less than 4 cm during the first year.Conclusion GnRHa treatment improves FAH efficiently for both CPP and EFP girls.Nevertheless,those who had menarche before treatment or whose growth velocity was less than 4 cm during the first year can hardly improve FAH by GnRHa treatment alone.

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.

Objective To investigate the possible mechanism of the effect of short-term gonadotropin-re-leasing hormone agonist(GnRHa)on linear growth in female pubertal rats. Methods Forty 3-week-old female rats were randomly divided into 5 groups(n=8 each). One group was sacrificed as base-line control. Group OVX was operated for ovariectomy at the beginning of experiment. Group Gn and group E2 each received two intramuscu-lar injections of 2.5mg·kg-1 triptorelin 2 weeks apart, and group E2 received additional daily 1μg·kg-1·d-1estradiol(E2)s. c. at three days after the second GnRHa injection for 11 days. Group Ctrl was sham-operated ascontrol. Each rat, except for the base-line control group. received 30mg/kg oxytetracycline s. c. and 20mg/kgcalcein s. c. 9 and 2 days respectively before sacrifice. Hepatic GH receptor mRNA, insulin-like growth factor(IGF)-I and IGF binding protein(IGFBP)-3, circulating IGF-I and IGFBP-3, local IGF-I/IGF-I receptor(IGF-IR)and proliferation rate(PFR)in epiphyseal growth plate(EGP)were evaluated after 4-week treatment.Results Similar to group OVX, the rats in group Gn became taller and heavier than group Ctrl with greater tibial length, wider EGP, greater longitudinal growth rate(LGR)and higher PFR(P<0.05 or P<0.01). Estrogen supplement reversed the effect of GnRHa. There was no statistical difference among the 4 groups regarding plasma IGF-I and IGFBP-3, hepatic IGF-I and IGFBP-3 mRNA levels, local IGF-I and IGF-I R levels in EGF. GnRHa down-regulated hepatic GHR mRNA expression, which was reversed by estrogen supplement. Conclusion GnRHa accelerates longitudinal growth of female pubertal rats. Estrogen deprivation contributes to GnRHa-induced alteration of linear growth in female rats, through improving PFR and suppressing the senescence of EGP. The underlying mechanism does not attribute to endocrine change of GH/IGF-I axis or local IGF-I/IGF-IR in EGP.

Objective To analyze the pattern of early catch-up growth In children with prepubertal short stature and various secretory forms of growth hormone(GH)following recombinant human growth hormone (rhGH)treatment and to explore the mechanism. Methods Sixty-two children with prepubertal short stature and various GH secretory forms were analyzed retrospectively, 27 with complete growth hormone deficiency (cGHD), 23 with partial growth hormone deficiency (pGHD)and 12 with idiopathic short stature(ISS). According to the GH peak value in GH provocative test, the group of pGHD was divided into pGHD-1(5.0-6.9μg/L)and pGHD-2(7.0-9.9μg/L). Height velocity, increase in height standard differentiation score (SDS), was calculated; serum levels of somatotrophic axis hormone were detected and bone age was determined. Results The quick early catch-up growth in different groups were similar in the initial 6 months. While that in the ISS group persisted for shorter period and was correlated with lower level in serum GH-binding protein(r=0.526,P=0.025)and Δinsulin-like growth factor-binding protein-3 (IGFBP-3) SDS (r=0.532,P=0.034) after rhGH treatment. The same doses of rhGH were applied to children with cGHD and pGHD. Children with pGHD-1 showed similar response to rhGH,regarding height velocity and ΔIGFBP-3 SDS, as compared with those of cGHD. However, children with pGHD-2 presented similar response with ISS, being worse than cGHD. Conclusion Downregulation of GH receptor and decrease in post-receptor effect seem to be the mechanism leading to early retardation in ISS. The incomplete catch-up growth in pGHD-2 may be caused by relatively inadequate rhGH dose. The cut-off value of GH provocative test in diagnosing GHD is more reasonable to be 7μg/L.

Objective To explore the relationship between adrenarche and gonadarche.Methods Total 49 idiopathic central precocious puberty(ICPP)girls,whose serum dehydroepiandrosterone sulfate(DHEAS)Z scores for chronological age were higher than+2 s at diagnosis.were enrolled.Physical examinations during pubertal stage were repeated at 3-6 months intervals,and serum DHEAS levels were monitored yearly within an average period of 4.08 years.Of them,16 girls were followed up until more than one year after discontinuation of gonadotropin-releasing hormone analogue(GnRHa)treatment.Results Before GnRHa treatment,these49 girls presented a younger average age at attainment of pubic hair stage2(PH2)and pubic hair stage3(PH3)than normal(8.07 years vs 11.16 years,8.82 years vs 12.40 years respectively).During GnRHa treatment,the intervals between PH2 and PH3,PH3 and pubic hair stage4(PH4),breast stage 2(B2),and PH2 were longer than normal(1.69 years vs 0.83 years,1.64 years vs 0.60 years,and3.62 years vs 0.76 years respectively).The intervals between PH2 and PH3,as well as B2 and PH2 during GnRHa treatment were also longer than that before GnRHa treatment(1.69 years/35 0.88 years,3.62 years vs 1.13 years respectively).The serum DHEAS Z scores decreased during GnRHa treatment,and increased significantly after GnRHa cessation.Conclusion Gonadarche after age of 6-year-old may lead to earlier adrenarehe.GnRHa treatment might slow down the progression of adrenarche and suppress the hypothalamuspituitary-gonadal axis.

Objective To evaluate the long-term final adult height outcome of combined treatment with gonadotropin-releasing hormone analogue(GnRHa)and recombinant human growth hormone(rhGH)in girls with idiopathic central precocious puberty(ICPP).Methods Out of 49 sirls with ICPP[treated with GnRHa at a dose of 60-80 μg/kg every 4 weeks for at least 6 months,whose height velocity fell below 4 cm/year and showed no improvement of predicted adult height(PAH)in 6 months],26 received(rhGH-combined group),in addition to chronological age,and duration of GnRHa treatment,who showed the same growth pattern but refused rhGH treatment,served to evaluate the efficacy of rhGH in addition.At the conclusion of the smdy,all the girls had been followed up for(3.3±1.9)years,and(3.2±0.9)years in rhGH-combined group and control group,respectively;and had achieved adult heisht.To compare the PAH with the final adult height(FAH)before and after treatment in the two groups.Results During rhGH treatment, height velocity of the rhGH-combined girls increased significantly[(6.7±2.0 vs <4)cm/year baseline],RhGH-combined gids showed an adult height far higher than pretreatment PAH [(157.5±4.5 vs 148.1±4.6)cm,P<0.01],and target height[(154.4±4.6)cm] was,significantly excceded.The control group reached an adult heisht also significandy higher than pretreatment PAH[(154.7±5.5vs 150.3±6.0)cm,P<0.01],while target height[(155.6±4.3)cm]was just reached but not significantlyexcceded.The gain in height obtained,calculated between pretreatment PAH and final heisat,(9.4±4.9)cm in rhGH-combined group was much more than that(4.3±4.2)cm in the control group(P<0.01).Conclusion RhGH may accelerate the linear growth and improve adult height of GnRHa-treated ICPP girls.

Objective To evaluate the association between two different linear growth patterns with the levels of serum insulin in children bem small for gestational age(SGA).Methods Serum fasting glucose,fasting insulin,and insulin-like growth factor-I(IGF-I)concentrations were determined in 30 catch-up growth(CUG)children bern SGA [CUG-SGA,16 females,14males,(6.62±0.66)year],37 non-catch-up growth(NCUG)children born SGA[NCUG-SGA,15 females,22 males,(5.97±0.56)year],and42 appropriate for gestational age(AGA)children with normal height[AGA,16females,26males,(7.05±0.39)year].Results (1) Basal fasting insulin and homeostasis model assessment for insulin resistance(HOMA-IR)were significantly higher in CUG-SGA group than in NCUG-SGA and AGA group(P<0.01 or P<0.05).But there was no difference in fasting insulin between NCUG-SGA group and AGA group.IGF-I levels in CUG-SGA were significantly higher than in NCUG-SGA group[(212.61±17.81 vs 137.40±14.66)ng/ml,P=0.001],but showed no difference from AGA group(P=0.095).(2)In the SGA group,HOMA-IR showed positive correlation with age,△height SDS,and current body mass index.Fasting insulin showed positive correlation with △height SDS(r=0.500,P=0.002)in≤6 year group as well as with △weight SDS(r=0.496,P=0.030)in>6 year group.Conclusions Insulin as a growth factor may participate in postnatal catch-up growth accompanied with increased insulin resistance in SGA children.