Do Most 7- to 8-Year-Old Girls with Early Puberty Require Extensive Investigation and Treatment?

Study ObjectiveTo investigate the etiology, progression, and treatment of precocious puberty in 7- to 8-year-old girls with breast development. Additionally, we evaluated the value of diagnostic tests in differentiating rapidly progressive precocious puberty (RP-PP) and slowly progressive precocious puberty (SP-PP) in these girls.DesignAmbispective cohort study.SettingSingle-center, pediatric endocrinology unit.ParticipantsGirls with breast development between the ages of 7 and 8 years and assessed between July 2016 and July 2018.InterventionsCollected of clinical data and followed-up for 2 to 3 years. Girls were divided into RP-PP and SP-PP groups.Main Outcome MeasuresDescribed the etiology, rate of progression of puberty, and proportion intervened and compared the results of auxiliary examinations between the groups.ResultsA total of 212 girls were enrolled, of which 211 (99.53%) were diagnosed with central precocious puberty (CPP) and 1 with peripheral precocious puberty (PPP). Hypophysis magnetic resonance imaging revealed that none had pathological brain lesions requiring surgical intervention. A total of 95 girls (44.81%) developed RP-PP, and 117 girls (55.19%) developed SP-PP. A total of 31 girls (14.62%) with RP-PP received treatment due to deteriorated predicting adult height. As compared with the SP-PP group, the RP-PP group showed more advanced bone age (BA), a higher level of basal luteinizing hormone (LH), and larger ovarian volume and uterine volumes. Receiver operating characteristic analyses revealed that BA was the best at identifying girls with RP-PP.ConclusionThe majority of girls with breast development between the ages of 7-8 years do not need treatment. BA is a useful preliminary test for identifying girls with RP-PP who are more likely to require treatment.     

Comparison of the Clinical and Anthropometric Features of Treated and Untreated Girls with Borderline Early Puberty

Study ObjectiveRisks associated with precocious puberty might be observed in the rapidly progressive form of borderline early puberty (BEP). Differentiating the rate of progression is important for deciding treatment with gonadotropin-releasing hormone analogue (GnRHa). The aim was to examine the treatment characteristics and effect of treatment on predicted adult height (PAH).DesignRetrospective observational study.SettingSingle-center, a pediatric endocrinology unit.ParticipantsA total of 135 girls, pubertal findings starting between 7-10 years of age.InterventionsData were collected via chart review. Patient groups were defined as treated with GnRHa (n = 63) or untreated (n = 72) girls.Main Outcome MeasuresReferral characteristics and anthropometric and pubertal findings of the patients with BEP, effect of treatment on PAH, and final height of the groups were compared.ResultsThe mean (±SD) age of the patients at admission and for the first appearence of pubertal findings was 8.8 ± 1.0 and 8.0 ± 0.8 years, respectively. Target height and PAH-target height values at admission were similar. At initiation of treatment, PAH of the treated girls (157.8 ± 7.2 cm) were significantly lower compared with untreated girls (160.7 ± 6.5 cm). The age at menarche of patients in the treated and untreated groups were 12.3 ± 1.0 and 11.3 ± 1.1 years, respectively. The final height of the groups were similar (157.1 ± 6.6 vs 157.0 ± 5.9 cm; P = .922) despite a lower PAH of the treated group.ConclusionGnRHa treatment resulted in an increase in PAH and normalized the age of menarche in patients with BEP. In selected girls with rapidly progressive BEP, GnRHa treatment may be considered.     

The effects of gonadotropin releasing hormone analogue therapy on girls with gonadotropin-dependent precocious puberty.

BACKGROUND/PURPOSE: It has been reported that gonadotropin releasing hormone analogue (GnRHa) therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. The purpose of this study was to evaluate the effect of GnRHa on the adult height of girls with gonadotropin-dependent precocious puberty and the adverse effects of such therapy. METHODS: Between 1989 and 2006, 11 girls with gonadotropin-dependent precocious puberty who had been treated with GnRHa and reached their adult height were enrolled in the present study. Follow-up studies of bone age, pelvic sonography and GnRH test were done regularly during the period of treatment. All patients had bone mineral density examined at least 2 years after completion of GnRHa therapy. RESULTS: GnRHa therapy was initiated at the age of 8.0 +/- 1.5 years. The predicted adult height immediately before GnRHa therapy was 146.7 +/- 4.8 cm (-2.3 +/- 0.9 standard deviation [SD]). The duration of GnRHa therapy was 4.7 +/- 1.8 years. The adult height of the patients was 156.3 +/- 4.3 cm (-0.6 +/- 0.8 SD), which is similar to their target height of 157.0 +/- 4.5 cm (-0.5 +/- 0.8 SD). The uterine sizes and gonadotropin responses to GnRH stimulation were well suppressed during treatment. Menstruation resumed 9.2 +/- 5.9 months after the discontinuation of treatment in these patients. Forty-five percent of patients had lumbar bone mineral density less than 1 SD below that of normal young Taiwanese adults in the Taipei region. CONCLUSION: GnRHa therapy can improve the adult height of patients with gonadotropin-dependent precocious puberty. However, 45% of patients had decreased bone accretion during therapy.     

Precocious Puberty: Changing Trends in Diagnosis and Treatment

Objective: the complications of precocious puberty may include premature menarche, shortened adult height due to accelerated bane maturation, and psychological distress. With advances in molecular biology and medical imaging techniques, and with a decade and a half of experience with the use of gonadotrophin-releasing hormone (GnRH) agonist analogue therapy to suppress central precocious puberty, the diagnosis and treatment of sexual precocity has been greatly refined. This paper discusses the recent advances in diagnostic and therapeutic interventions for central precocious puberty in girls, with emphasis on the following outcomes: final adult height, ovarian function, and psychological sequelae.Methods: we reviewed the literature on the diagnosis and therapy of precocious puberty. Data were abstracted from reports that included outcome measures of final adult height, ovarian/menstrual function or psychological assessments in treated and untreated female patients.Results: most reports demonstrate increased final adult height in women treated with GnRH analogues when compared to reports of untreated patients or those treated with cyproterone acetate or medroxyprogesterone acetate. This effect appears to be most marked in patients with extremely precocious pubertal onset, before age five to six years. Menarche occurs within two years of treatment cessation in nearly all patients. Limited data exist regarding the psychological consequences of sexual precocity or its treatment.Conclusion: GnRH analogues have become the treatment of choice for girls with central precocious puberty. Their ability to suppress chronically the central activation of the hypothalamic-pituitary-ovarian axis represents a major advance, and results in the slowing of bone maturation and the reversible delay of menarche and the progression of secondary sexual characteristics.     

不同初治年龄对先天性肾上腺皮质增生症患儿发育的影响

目的了解不同初治年龄对先天性肾上腺皮质增生症(CAH)患儿身高、骨龄、性早熟等方面的影响。 方法将1982~2004年在上海新华医院和上海市儿科医学研究所内分泌、遗传代谢病专科诊治的32例CAH患儿(年龄：女≥8岁，男≥9岁)，按初治年龄分为≤3岁组(14例)和>3岁组(18例)，观察两组间末次复诊时骨龄与身高龄之差、性早熟例数及男女患儿发生性早熟的不同。 结果14例初治年龄≤3岁患儿末次复诊时骨龄与身高龄之差\[(30±20)岁\]与18例>3岁组\[(46±16)岁\]比较差异有显著性(P<005)，初治年龄>3岁组发生真性性早熟(9例)与≤3岁组(2例)比较差异有显著性(χ2=4453，P<005)。男性患儿发生真性性早熟(9例)与女性患儿(2例)比较差异有显著性(χ2=4794，P<005)。 结论CAH患儿≤3岁得到诊治者其预测终身高较>3岁方诊治者明显改善，其性早熟发生率明显减少，男性CAH患儿较女性CAH患儿更易发生性早熟。     

促性腺激素释放激素类似物（曲普瑞林）治疗女童特发性中枢性性早熟23例疗效观察

目的观察促性腺激素释放激素类似物（曲普瑞林）治疗女童特发性中枢性性早熟（ICPP）的临床疗效。方法应用曲普瑞林治疗23例ICPP女童6个月,观察治疗前后第二性征、子宫、卵巢、骨龄（BA）、血清雌二醇（E2）、促性腺激素释放激素（GnRH）激发试验激素水平、预测成人终身高的变化及药物副反应。结果治疗后患儿乳房、子宫、卵巢体积均有缩小,E2、促黄体生成激素（LH）、卵泡刺激素（FSH）峰值均显著降低,骨龄成熟延迟,骨龄/实际生活年龄（BA/CA）值下降,预测成人终身高治疗前为（155.5±0.81）cm,治疗后为（157.0±0.81）cm,较治疗前有改善,差异具有统计学意义（P〈0.01）。结论曲普瑞林治疗ICPP能够抑制性腺轴及性腺发育,延缓BA成熟,最终对改善成人终身高有意义。     

简化促性腺激素释放激素兴奋试验在女性同性性早熟症诊断中的应用

目的 探讨简化促性腺激素释放激素(GnRH)兴奋试验用于女性同性性早熟症发病原因的诊断及指导治疗的价值。方法 对42例女性同性性早熟患者施行简化GnRH兴奋试验,其中38例患者平均随访26(3～78)个月,观察患者的临床表现及病情发展情况。结果 42例患者对GnRH兴奋试验反应分为黄体生成激素(LH)优势型、卵泡刺激素(FSH)优势型及无反应型3类。其中LH优势型14例(33％,14/42),包括下丘脑错构瘤1例、特发性性早熟13例;14例中生长过速或骨成熟过早各10例。FSH优势型13例(31％,13/42),包括生长过速2例、骨成熟过早1例。无反应型15例(36％,15/42),8例为外周性性早熟症,包括卵巢颗粒泡膜瘤1例、自主性功能性卵巢滤泡囊肿2例、McCune-Albright综合征2例、外源性性早熟症3例;15例中生长过速4例、骨成熟过早5例。FSH优势型13例及无反应型的其余7例,未发现明确的发病原因,考虑为一过性性早熟症或乳房早发育。结论 简化GnRH兴奋试验有助于女性同性性早熟症发病原因的诊断,及客观判断下丘脑-垂体-卵巢轴是否被激活,较临床指标更为可靠。     

Precocious puberty: a comprehensive review of literature

CONTEXT: Precocious puberty currently affects 1 in 5,000 children and is 10 times more common in girls. Statistics indicate that girls in the United States are maturing at an earlier age than they did 30 years ago and the number of girls with diagnosed precocious puberty (the appearance of secondary sex characteristics before 8 years of age or the onset of menarche before age 9) is on the rise. A summary of the growing body of literature on this topic is necessary to inform nurses and other health care providers of the current trends and incidence of precocious puberty to better meet the physical and psychosocial needs of these girls and their families. METHODS: EBSCOhost Research Databases that included CINAHL Plus, Health Source: Nursing Edition, MEDLINE, PsycINFO, and Women's Studies International were searched for journal articles published in the past 10 years (1997-2006) that explicitly examined precocious puberty in females and proposed theories to describe the phenomenon. Search terms included precocious puberty, sexual maturation, menarche, and secondary sex characteristics. These terms were searched individually and in combination with proximate determinants such as endocrine disruptors, environmental toxins, phthalates, stress, skin care, genetics, age, ethnicity, obesity, and assisted reproduction. The search yielded 947 articles addressing this issue. RESULTS: Eighty-two studies or case reports met the criteria for inclusion in this literature review that captured six attributable causes of early sexual maturation in female children. These included genetic, ethnic, and pediatric obesity, as well as environmental toxins that disrupt endocrine function (chemicals, toxins, plasticizers, infant feeding methods, skin and hair products, assisted reproductive technologies), psychosocial stress, and early exposure to a sexualized society. The robustness of the reports varied and few of the studies were widely generalizable but did offer suggestions for assessment and nursing care. CONCLUSIONS: Precocious puberty has health and social implications that are complex and influenced by multiple factors. Further research is needed to expand and elucidate theoretical relationships between the early development of secondary sex characteristics in young girls and the proposed causative factors.     

中国城市儿童性早熟现状的调查研究

目的对国内城市儿童性早熟现状进行调查,为制定有效的预防策略,并推动儿童性早熟的临床规范化和个性化治疗提供理论依据。方法 2014年3月至12月在全国范围内开展"中国城市儿童性早熟现状调研"活动。调研共收集来自全国10余省市的2 687份问卷,其中1 714份问卷纳入统计分析。结果调查人群大多分布在全国10个主要省市,包括北京、上海、重庆、江苏、湖北等;调查患儿以女童为主,其男女比例约1∶16。诊断为中枢性性早熟的患者占75.79%(1 299/1 714);调查中初次诊断为中枢性性早熟患者占88.91%(1 524/1 714)。调查患者的骨龄为(10.00±1.77)岁,高于实际年龄(8.29±1.60)岁,差异有统计学意义(P0.001);初次诊断为CPP的患者的骨龄为(10.11±1.70)岁,高于实际年龄(8.35±1.57)岁,差异均有统计学意义(P0.001)。结论国内城市儿童性早熟就诊患者的年龄偏大,为防止患者就诊时已错过最佳的干预和治疗时机,应引起对疾病筛查的高度重视,做到早发现、早诊断和早治疗。     

Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls.

Children born small for gestational age (SGA) may present advanced bone maturation in childhood and reduced final height. The objectives of the study were to evaluate adrenarche, pubertal development, age at menarche and final height in full-term born-SGA girls. Twenty-four girls (12 born-SGA and 12 matched controls) were evaluated at 6-7.5 years of age for clinical signs of puberty and dehydroepiandrosterone sulfate (DHEAS) levels, as a marker of adrenarche. Thirty-eight girls (19 born-SGA and 19 matched controls) were evaluated at 17.5-18.5 years of age to assess final height, sexual maturation and age at menarche. SGA girls had a mean final height (160.1 cm vs 165.8 cm, p < 0.01) and mean weight (52.1 kg vs 56.5 kg, p < 0.05) significantly lower than controls. Controls had a mean final height significantly higher than their mean target height. Sexual maturation was at stage 5 of Tanner's staging in SGA girls and control subjects. SGA girls had a slightly anticipated puberty (9.9 vs 10.4 years for initial breast development) and a lower age at menarche (11.9 vs 12.3 years). At 6-7.5 years of age, SGA females and controls did not show any difference for clinical signs of puberty; however, DHEAS levels (0.75 + 0.18 microgram/ml vs 0.57 + 0.22 microgram/ml, p < 0.05) were significantly higher in SGA girls than in control subjects. We concluded that full-term born-SGA females have impaired final height and weight in adolescence but substantially normal sexual maturation and age at menarche. Increased DHEAS levels before puberty in born-SGA girls may predispose to increased bone maturation in childhood with a reduced final height. In our population a progressive increment in final stature is evident.     

Primary hypothyroidism presenting as ovarian tumor and precocious puberty in a prepubertal girl

We report a case of a prepubertal girl with juvenile primary hypothyroidism presenting as ovarian cysts and precocious puberty. The 7-year-old female was referred to our clinic because of a pelvic/abdominal mass and vaginal bleeding. Besides these findings, on physical examination we noticed the thyroid gland globally increased and the presence of secondary sexual characteristics. Based upon the clinical profile and investigations, the patient was diagnosed with juvenile primary hypothyroidism due to autoimmune thyroiditis. The cysts and precocious puberty resolved spontaneously after the simple replacement of thyroid hormone. It is important to bear in mind hypothyroidism in cases of girls presenting ovarian cysts and precocious puberty in order to avoid unnecessary surgery on the ovaries.     

Adrenarche,pubertal development,age at menarche and final height of full-term,born small for gestational age (SGA) girls

Children born small for gestational age (SGA) may present advanced bone maturation in childhood and reduced final height. The objectives of the study were to evaluate adrenarche ,pubertal development ,age at menarche and final height in full-term born-SGA girls. Twenty-four girls (12 born-SGA and 12 matched controls) were evaluated at 6-7.5 years of age for clinical signs of puberty and dehydroepiandrosterone sulfate (DHEAS) levels ,as a marker of adrenarche. Thirty-eight girls (19 born-SGA and 19 matched controls) were evaluated at 17.5-18.5 years of age to assess final height ,sexual maturation and age at menarche. SGA girls had a mean final height (160.1 cm vs 165.8 cm ,p < 0.01) and mean weight (52.1 kg vs 56.5 kg ,p < 0.05) significantly lower than controls. Controls had a mean final height significantly higher than their mean target height. Sexual maturation was at stage 5 of Tanner's staging in SGA girls and control subjects. SGA girls had a slightly anticipated puberty (9.9 vs 10.4 years for initial breast development) and a lower age at menarche (11.9 vs 12.3 years). At 6-7.5 years of age ,SGA females and controls did not show any difference for clinical signs of puberty; however, DHEAS levels (0.75 + 0.18μg/ml vs 0.57 + 0.22μg/ml ,p < 0.05) were significantly higher in SGA girls than in control subjects. We concluded that full-term born-SGA females have impaired final height and weight in adolescence but substantially normal sexual maturation and age at menarche. Increased DHEAS levels before puberty in born-SGA girls may predispose to increased bone maturation in childhood with a reduced final height. In our population a progressive increment in final stature is evident.     

Serum Makorin ring finger protein 3 values for predicting Central precocious puberty in girls

This study evaluated the serum level of MKRN3 and investigated its diagnostic usefulness in girls with central precocious puberty (CPP). In total, 41 girls with CPP and 35 age-matched normal control girls were enrolled. Serum values of MKRN3 were measured in both groups. Gonadotropin and estradiol concentrations were evaluated after 6 and 12?months of GnRH agonist (GnRHa) treatment in CPP patients. The MKRN3 concentrations were much lower in the patient group than in the control group (p?=?.005). Over 1 year of GnRHa treatment in patients, the gonadotropin concentrations were significantly decreased (p?<?.05), while the MKRN3 concentrations were unchanged (p?>?.05). MKRN3 levels were inversely correlated to standard deviation (SD) in height (r?=??0.46, p?=?.000), SD in weight (r?=??0.32, p?=?.005), Tanner stage (r?=??0.41, p?=?.000), and bone age (r?=??0.46, p?=?.000). Based on ROC analysis, the area under curve was 0.758 for MKRN3, with 82.9% sensitivity and 68.5% specificity. The measurement of serum MKRN3 level may provide some help for CPP prediction, but relatively various values need further validation     

Age at Pubertal Development in a Hispanic-Latina Female Population: Should the Definitions Be Revisited?

Study ObjectiveTo assess pubertal events in a Hispanic female population and to create normograms of puberty.DesignLongitudinal.SettingUniversity facility.ParticipantsFive hundred forty-nine girls from the Growth and Obesity Chilean Cohort study.InterventionsFollow-up twice a year beginning at age 6 years.Main Outcome MeasuresBreast development, pubic hair development, and age. Breast development (B2, B3, and B4) and pubarche (P2) were determined. Age at menarche was obtained from the adolescents and their mothers. Age and growth velocity at peak height velocity were calculated.ResultsIn girls, B2, B3, and B4 occur at median ages of 9.2, 10.2, and 10.9 years, respectively. The median age at P2 was 9.7 years. The mean age at peak height velocity and the growth velocity were 10.6 years (SD = 1.1) and 8 cm/y, respectively. The mean age at menarche was 11.9 years (SD = 1.1); only 2.8% (15 /530) of girls experienced menarche after 14 years and 1.9% before 10 years. The mean interval time between B2 and menarche was 2.5 ± 1.0 years. Transient thelarche occurred in 8.6% of girls.ConclusionThis longitudinal cohort shows that thelarche occurred 1.2 months later than previously reported in cross-sectional studies. Conversely, we found that pubic hair appeared 12 months earlier and menarche occurred 9 months earlier than previously reported. These findings are important in setting normalcy data and avoiding unnecessary clinical consultations.     

Evaluation of melatonin on the precocious puberty: a pilot study

Objective. To evaluate the effect of 6-sulphatoxymelatonin on the sleep quality of girls with precocious puberty. Study design. Ninety-nine girls were divided into three groups: GI, precocious puberty; GII, normal prepubescent; GIII, normal puberty. Questionnaires containing demographic and clinical data were applied. Blood was collected for hormonal evaluation for 6-sulphatoxymelatonin. The modified Rush Sleep Diary was used. Results. The levels of 6-sulphatoxymelatonin were highest in the group without pubertal development (75.23?±?10.84?ng/ml), second highest in the group with normal puberty (45.66?±?3.87?ng/ml, p?<?0.001) and lowest in the group with true precocious puberty (37.04?±?5.47?ng/ml). The amount of day sleep was greater in the group without pubertal development compared to other groups. Conclusion. Despite the sleep data, melatonin may be involved in the precocious puberty process.     

Insight: prolonged vaginal bleeding during central precocious puberty therapy with a long-acting gonadotropin-releasing hormone agonist: a proposed mechanism and management plan

We have previously described our data collected after administration of gonadotropin releasing hormone-agonist (GnRH-a) to delay sexual maturation, in premenarchal girls suffering from idiopathic central precocious puberty.¹ We have explained the recurrent episodes of bleeding due to discontinuation of the estrogen support of the proliferative and stable endometrium. The recognition in recent years of the extra-pituitary functions of GnRH-a, the ability of GnRH to stimulate prostaglandin production and the known role of prostaglandins in irregular vaginal bleeding prompted us to seek alternative explanations to our data.We suggest considering a potential clinical use of combination therapies of GnRH agonists and prostanoid receptor antagonists to treat central precocious puberty.     

2~10岁性早熟女童骨密度检测分析

目的探讨性早熟对2~10岁女童骨密度的影响。 方法选择2003 01—2006 01在湖南省儿童医院内分泌专科就诊的2~10岁性早熟(明确诊断、并排除影响骨代谢性疾病)女童237例，根据真、假性性早熟(CPP、PPP)分为2组，各组再按年龄组分层，采用单光子骨矿物质密度测定仪测量左手桡骨中远1/3处桡、尺骨密度(BMD)，并与同龄健康女童进行对比和分析。 结果CPP、PPP和健康组BMD均随年龄增长而增加，3组各年龄桡骨BMD均高于尺骨；CPP桡、尺骨BMD均相对较高，8~10岁组中CPP较对照组约高6.4%~8.6%；3组桡、尺骨BMD均在8~10岁增长加速，特别是尺骨(P<0.05)，分别较6~7岁组增长20.4%、17.8%和14.3%；以CPP组增幅最大，明显高于健康组，与健康组(6~7岁)增长比较差异有显著性(桡骨P<0.05、尺骨P<0.001)。PPP组则与健康女童差异不显著。 结论健康女童骨矿化自9岁起开始青春期加速，CPP女童青春期尺骨生长加速的年龄提早，BMD相应增加，而PPP不像CPP那样明显影响女童的正常骨骼发育。     

Inhibin B as a screening tool for early detection and treatment monitoring of central precocious puberty

Abstract

Anti-Müllerian hormone (AMH) and inhibin B are considered possible biomarkers of central precocious puberty (CPP). The aim of this study was to evaluate serum levels of AMH and inhibin B, to investigate their regulatory patterns, and to study their clinical significance in girls with CPP. In total, 48 girls with CPP and 35 age-matched prepubertal control girls were enrolled in the study. AMH and inhibin B levels were determined in the CPP and control groups. In the patient group, AMH and inhibin B levels were evaluated during 1?year of gonadotropin releasing hormone analog (GnRHa) treatment. The mean inhibin B level in the CPP group was significantly higher than that in the control. AMH levels were not different between the two groups. After GnRHa treatment. AMH and inhibin B levels decreased significantly. Based on the ROC analysis, the cutoff value for inhibin B to determine CPP was 19.59?pg/mL, with 83.3% sensitivity and 82.9% specificity, and the area under the curve was 0. 852. Inhibin B was useful for determining CPP and the therapeutic effects of GnRHa treatment in girls with CPP. AMH interacted, in part, with the hypothalamo-pituitary gonadal axis, but its clinical implications in CPP should be further investigated.     

Anti-Müllerian hormone as a possible predictor of fecundability in subfertile women over 38 years: a retrospective cohort study

Constitutional delay of puberty (CDP) in otherwise healthy girls is defined as failure to develop secondary sexual features past the age of 13 years (two standard deviations above the mean age at which secondary sexual features appear in the population of girls). The inhibitory action of neuropeptide Y (NPY) on the gonadotropic and somatotropic systems in experimental animals and stimulation by NPY of the hypothalamic–pituitary–adrenal axis have been reported, prompting us to study the levels of NPY, insulin-like growth factor-I (IGF-I) and cortisol in eight girls with CDP and normal weight (body mass index (BMI) 21.7?±?4.5?kg/m²). The results were compared with those from a group of 40 girls (BMI?=?20.0?±?3.1?kg/m²) who demonstrated a normal course of puberty (NP). All girls were studied at menarche (mean age at menarche, study vs. control: 16.4?±?0.7 vs. 12.6?±?0.9 years). To measure NPY and IGF-1 we used a radioimmunoassay method, whereas cortisol was measured with an enzyme immunoassay. Blood was collected between 08.00 and 09.00 following an overnight fast. NPY was higher in girls with CDP (181.6?±106.4?pg/ml) than in girls with NP (55.5?±?26.3?pg/ml; p?<?0.001). In the former group, cortisol was higher (397.3?±?241.6?nmol/l) than in NP girls (142.7?±98.0?nmol/l; p?<?0.01). Levels of IGF-I in CDP girls were lower than in NP girls (558.0?±?122.6 vs. 756.5?±?226.8?ng/ml; p?<?0.01). The results corroborate the involvement of NPY in sexual maturation and its role in delayed puberty.     

中枢性性早熟患儿5种骨龄测定方法的比较研究

目的探讨CHN法、TW2法中日英3种标准、TW3法5种骨龄测定方法对中枢性性早熟（CPP）患儿的诊断价值及正常值临界点的确定。方法由两名医师采用盲法回顾性分析CPP患儿61例（病例组）,与每一个CPP患儿性别相同,年龄、身高、体质量基本一致的同期体检者61例、8岁以后出现乳房发育的女童6例（均为对照组）治疗前左手腕部X线片,用CHN法、TW2法中英日3种标准和TW3法进行骨龄判定,计算骨龄与年龄的差值,用SPSS13.0统计软件进行受试者工作特征（ROC）分析。结果 （1）两名医师骨龄测定结果的Kappa值为0.776（u=16.128,P〈0.05）;（2）5种骨龄测定方法的ROC曲线下面积分别为：CHN法0.921±0.024,95%可信区间为0.875～0.967;TW2法中国南方人标准为0.947±0.019（0.910～0.983）;TW2法日本人标准为0.937±0.023（0.892～0.982）;TW2法英国人标准为0.931±0.022（0.888～0.975）;TW3骨龄测定法为0.924±0.023（0.879～0.969）;5种方法的诊断价值差异无统计学意义（Z=0.85,P〉0.05）;（3）CHN中骨龄与年龄的差值≥1.25岁、TW2-CHN中差值≥1.25岁、TW2-JP中差值≥0.65岁、TW2中差值≥1.15岁、TW3中差值≥0.25岁,敏感度、特异度均较高。结论 5种骨龄测定方法对于中枢性性早熟患儿的诊断价值都较高;而TW2法中国人标准（TW2-CHN）的诊断价值最高。