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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。     

Etiology of central precocious puberty in males: the results of the Italian Study Group for Physiopathology of Puberty

We reviewed the hospital records of 45 boys, followed in 13 pediatric departments throughout Italy, who had undergone computed tomography and/or magnetic resonance imaging for central precocious puberty (CPP). Twenty-seven patients (60%) had idiopathic CPP and 18 (40%) neurogenic CPP. A hamartoma of the tuber cinereum was found in six patients (33%). All patients with hypothalamic hamartoma had earlier onset of symptoms than patients with idiopathic CPP. Five patients (27%) were affected by type 1 neurofibromatosis, two had ependymoma and five patients had an intracranial anomaly. Basal LH and basal and peak LH/FSH ratio were greater, but not significantly, in boys with neurogenic CPP than in boys with idiopathic CPP. The highest LH peak levels were observed in patients with hamartoma; however, no correlation was observed between LH peak and the size of the hamartomas. In addition, bone age at diagnosis was more advanced in patients with hamartoma than in patients with other conditions. In conclusion, gonadotrophin-dependent precocious puberty may be of idiopathic origin or may occur in association with any CNS disorder. Further studies are needed in order to evaluate the effects of nutritional, environmental and psychosocial factors on the timing of sexual maturation, to explain the high incidence of idiopathic CPP in our male patients.     

Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.     

Idiopathic central precocious puberty in girls: presentation factors

Background  

It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP).     

The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty

OBJECTIVES: To assess the value of gonadotrophin releasing hormone (GnRH) stimulation test in identifying intracranial abnormality in girls with central precocious puberty (CPP). PATIENTS AND METHODS: A study of 67 girls diagnosed with CPP who underwent cranial MRI scans. Patients were not receiving any therapy and there were no neurological signs or symptoms at presentation. Patients underwent evaluation of GnRH stimulation test and plasma oestradiol levels at presentation. RESULTS: Mean age at onset of puberty was 6.2 years (range 2.0 to 8.0 years). Intracranial abnormalities were present in 10 (15%) patients, while 57 girls (85%) had no abnormalities. No significant difference was shown between girls with intracranial abnormality and girls without intracranial abnormality in basal LH or FSH values, peak LH or FSH values, LH/FSH peak ratios, peak LH/basal LH ratios, peak FSH/ basal FSH ratios at presentation. CONCLUSION: GnRH stimulation test does not identify those with underlying intracranial abnormality at presentation. MRI imaging remains necessary in all cases of central precocious puberty in girls.     

Predictive factors for organic central precocious puberty and utility of simplified gonadotropin-releasing hormone tests

BACKGROUND: The aim of the present study was to determine whether the clinical presentation of patients with central precocious puberty (CPP) permits differentiation between idiopathic and organic forms, and to examine whether luteinizing hormone (LH) determination in single blood sample after gonadotropin-releasing hormone (GnRH) administration is sufficient to diagnose CPP. METHODS: Potential clinical and laboratory predictors for the presence of central nervous system (CNS) abnormalities were assessed. Sensitivities and specificities of LH and follicle-stimulating hormone (FSH) levels at 0, 15, 30, 60, 90 and 120 min were compared after GnRH stimulation. RESULTS: In 45 girls with signs of breast development, 26 were diagnosed as having CPP. The age of onset in patients with organic CPP was 4.75 +/- 2.01 years (range 1.2-7.1 years, median 5.0 years), whereas the age in patients with idiopathic CPP was 7.09 +/- 0.87 years (range 5.0-7.9 years, median 7.0 years). This parameter is the only one showing statistical significance. In addition, the specimen at 30 min after GnRH stimulation yielded highest sensitivity for the diagnosis of CPP. CONCLUSIONS: The earlier the onset of disease, the higher the possibility of presence of CNS lesion. According to the mean GnRH-stimulated LH levels and sensitivity at each time, a single blood sample obtained for LH determined after GnRH administration at 30 min can be used to diagnose CPP.     

Central precocious puberty

Diagnosis of the central origin of precocious puberty is easy in boys on the enlargement of the testes. In girls, conversely, diagnosis of central precocious puberty (CPP) may be difficult, as isolated development of the breast may initially be the only feature. Differentiation of CPP and premature thelarche is nevertheless essential, as CPP always requires neuroradiologic investigations to look for an intracranial space-occupying lesion and may indicate inhibitory treatment. CPP is usually idiopathic in girls and tumor-related in boys. Early secretion of sex steroids increases the rate of growth and bone maturation and may lead to final short stature. LHRH analogues represent a breakthrough in the treatment of CPP.     

Precocious puberty

Puberty occurring before the age of 8 years in girls and 9 years in boys is considered precocious. The numerous causes of precocity can be classified as central or peripheral. Central or true precocious puberty (CPP) is due to premature activation of the hypothalamopituitary-gonadal axis and is isosexual. Peripheral or pseudoprecocious puberty (PPP) results from the production of sex steroids independent of the H-P-G axis and may be isosexual or heterosexual. CPP is the most common form of precocity involving more than 50% of children and is much more common in girls than boys. CPP is more common between 4 and 8 years. A peak serum LH levels >10 iu/1 following GnRH stimulation is the absolute evidence of CPP. Serum IGF-I levels are predictive of the outcome. Availability of CT and MRI has helped to determine the cause of CPP in most cases. Hypothalamic hamartoma is the most common tumour causing CPP especially in boys. Adrenal causes, particularly CAH, are the commonest cause of PPP in boys whereas ovarian causes are more likely in girls. Long acting GnRH analogues provide a safe and effective form of treatment of CPP.     

Cranial MRI scans are indicated in all girls with central precocious puberty.

AIMS: (1) To assess the value of cranial magnetic resonance imaging (MRI) scans in the investigation of girls with central precocious puberty (CPP); and (2) to determine the clinical predictors of abnormal cranial MRI scans in these patients. METHODS: A retrospective study of 67 girls diagnosed with CPP who underwent cranial MRI scans at diagnosis. Patients with neurological signs or symptoms at presentation were excluded. RESULTS: The mean age of onset of puberty was 6.2 years (range 2.0-7.9). Intracranial abnormalities were present in 10 (15%) patients (MR+), while 57 (85%) had no abnormalities (MR-). There was no statistical difference between MR+ patients and MR- patients at presentation with respect to age of onset of puberty, pubertal stage, bone age advance, pelvic ultrasound findings, or height or body mass index standard deviation scores (SDS). CONCLUSION: Girls with CPP should have a cranial MRI scan as part of their assessment since clinical features, including age, are not helpful in predicting those with underlying pathology. Implementation of such an approach may have a substantial effect on clinical practice and healthcare cost.     

Central precocious puberty: epidemiology, etiology, diagnosis and treatment

Central precocious puberty (CPP) is a rare disease with female predominance and a higher incidence among adopted children. Of idiopathic aetiology in most cases, in the past few years the first mutations in patients with CPP have been described. The prevalence of organic disease is notably lower among girls with CPP. However, no predictors have been described to select which kind of girls should undergo an imaging tests. Although the sensitivity of the determination of basal LH as a marker of CPP has improved with the new techniques, to date, the LH peak after LHRH stimulation test remains the gold standard for the diagnosis of CPP. Finally, the use of GnRH analogues has shown to be particularly effective in the treatment of CPP patients less than 6 years-old.     

Cranial MRI scans are indicated in all girls with central precocious puberty

Aims: (1) To assess the value of cranial magnetic resonance imaging (MRI) scans in the investigation of girls with central precocious puberty (CPP); and (2) to determine the clinical predictors of abnormal cranial MRI scans in these patients. Methods: A retrospective study of 67 girls diagnosed with CPP who underwent cranial MRI scans at diagnosis. Patients with neurological signs or symptoms at presentation were excluded. Results: The mean age of onset of puberty was 6.2 years (range 2.0–7.9). Intracranial abnormalities were present in 10 (15%) patients (MR⁺), while 57 (85%) had no abnormalities (MR^-). There was no statistical difference between MR⁺ patients and MR^- patients at presentation with respect to age of onset of puberty, pubertal stage, bone age advance, pelvic ultrasound findings, or height or body mass index standard deviation scores (SDS). Conclusion: Girls with CPP should have a cranial MRI scan as part of their assessment since clinical features, including age, are not helpful in predicting those with underlying pathology. Implementation of such an approach may have a substantial effect on clinical practice and healthcare cost.     

Causes and Types of Precocious Puberty in North-West Iran

Objective

Precocious puberty is of concern because of the underlying disorders, the short adult stature, and the psychosocial difficulties. This study was carried out in order to evaluate the characteristics of children referred to pediatric endocrinology clinic with diagnosis of precocious puberty.

Methods

In a cross-sectional study between February 2007 and September 2009, all of the children referred to pediatric endocrinology clinic in North-West Iran with diagnosis of precocious puberty were recruited.

Findings

Data of 106 girls (82.2%) and 23 boys (17.8%) were analyzed. Mean age of the patients at the time of referral was 6.6±2.8 years (ranging 0.3-14 yr), which was 7±3.9 (ranging 0.3-14 yr) for boys and 6.6±2.5 (ranging 0.8-12 yr) for girls (P=0.6). Out of 129 subjects, 56(43.4%) had precocious puberty, 71.4% (35 cases) of them were due to central precocious puberty and 28.6% (16 cases) were pseudo-precocious puberty. 73 out of 129 subjects (56.6%) were due to normal variants of puberty, normal puberty, and no puberty. 87.5% of subjects with central precocious puberty were idiopathic.

Conclusion

Most of children referred with diagnosis of precocious puberty have benign normal variants. Most of cases with precocious puberty are affected with central precocious puberty, especially with idiopathic form of it.     

Optimal therapy of pubertal disorders in precocious/early puberty

GnRHa have been used in the treatment of central precocious puberty (CPP) for a decade and some final results of this therapy are now available. Treatment preserves height potential in younger patients and a complete recovery of the hypothalamic-pituitary-gonadal axis occurs at the end of treatment. However, some aspects of the management of CPP are still debated. Probably the age limits between normal and precocious puberty have to be lowered, and new diagnostic tools will modify and simplify diagnostic criteria. The possibility of progression of premature thelarche into precocious puberty, the pathogenesis of organic and idiopathic precocious puberty, the criteria for decision to treat and to stop treatment and the utility of an association with GH treatment will be better understood in the future. Follow-up of patients after stopping therapy includes frequency and characteristics of menses, the possible higher incidence of polycystic ovary-like syndrome and the correct achievement of a normal peak bone mass and body composition. In this review we discuss some of these points, with particular attention to precocious puberty in girls.     

女童全身体脂比率与性早熟的关系

目的 既往研究提示体重指数（BMI）与女童发育年龄有关,但是否与女童全身脂肪比率相关尚不清楚。该研究旨在分析全身脂肪比率与性早熟的关联性。方法 依据中枢性性早熟诊断与治疗共识将2017年7~8月收治的128例性早熟患儿分为中枢性性早熟组（CPP组,87例）和外周性性早熟组（PPP组,41例）,同时纳入51例未发育女童作为对照组。利用双能X线吸收测量法检测上肢组织、腿部组织、躯干组织、男性区、女性区和全身组织的脂肪比率,结合研究对象的年龄、BMI、BMI-Z值、骨龄、卵巢体积、激素水平等实验室检查结果,综合分析脂肪比率和性早熟的相关性。结果 与对照组比较,CPP组和PPP组患儿上肢、腿部、躯干、男性区、女性区和全身组织的体脂率参数以及腿部/全身脂肪比和（上肢+腿部）/躯干脂肪比均显著升高（均P < 0.05）,而上述所有体脂率和脂肪分布指标在CPP组和PPP组间比较差异均无统计学意义（均P > 0.05）。在性早熟女童中,高体脂率组的黄体生成素（LH）基础值及黄体生成素释放激素（LHRH）激发试验的LH峰值、LH/卵泡刺激素峰值均显著高于低体脂率组,差异均有统计学意义（均P < 0.05）。同时高体脂率组和低体脂率组LH基础值相比于对照组均显著升高（均P < 0.05）。结论 体脂含量的增加可能是诱发女童性早熟的因素,但具体机制尚有待进一步研究。     

Efficacy of combined treatment with growth hormone and gonadotropin releasing hormone analogue in children with poor prognosis of adult height

OBJECTIVE: This study was conducted to study the role of combination therapy of growth hormone and Gonadotropin-releasing hormone (GnRH) analogues in girls with idiopathic central precocious puberty (CPP) or idiopathic short stature (ISS). METHODS: Five girls with CPP (median age 9.1 y, pubertal stage 2-3) (3 of them previously treated with GnRH analogue (GnRHa) for 16.2 +/- 0.3 months) and 8 girls with ISS (median age 11.4 y, pubertal stage 2-3) (previously treated with GH for 10.95 +/- 1.42 months), were treated with recombinant human GH (0.33 mg/kg/week) and GnRHa (3.75 mg/28 days) for 22 months. RESULTS: Height of girls with CPP improved from - 1.3 to - 0.2 SDS and height for BA from - 2.1 to - 0.6 SDS (P = 0.042). Predicted adult height (PAH) improved from - 3.1 to - 0.6 SDS (P = 0.042). In girls with ISS only PAH improved from - 3.0 to - 1.5 SDS (P = 0.025). CONCLUSION: Combined treatment improves height and PAH in CPP. Height in ISS is also improved however not significantly.     

A study of anthropomorphic and biochemical characteristics in girls with central precocious puberty and thelarche variant

BACKGROUND: Premature thelarche in later childhood may progress to central precocious puberty (CPP), which does not spontaneously resolve. Thelarche variant (TV) is a slowly progressive variant of precocious puberty. AIM: To determine and compare levels of insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) and anthropomorphic measures in girls with TV and CPP. SUBJECTS: Prepubertal controls and girls with TV and CPP. METHODS: Chronological and bone age, weight, height, BMI, height velocity (HV), and serum IGF-I, IGFBP-3, leptin, follicle-stimulating hormone (FSH) and lutenizing hormone (LH) levels were assessed. RESULTS: Serum IGF-I levels, HV and IGF-I/ IGFBP-3 ratio were significantly higher in girls with CPP compared to both controls and girls with TV. IGFBP-3 values for bone age (IGFBP-3BA) were significantly higher in the TV group compared to both controls and girls with CPP. FSH and LH concentrations were significantly higher in the CPP group compared to TV. CONCLUSION: HV, IGF-I, LH and FSH levels and IGF-I/IGFBP-3 ratio are elevated in girls with CPP compared to those with TV.     

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 in girls with premature thelarche

Premature thelarche (PT) is characterised by precocious breast development without any other sign of puberty, normal height velocity (HV) and normal bone maturation, while girls with central precocious puberty (CPP) show increased HV, bone maturation and increased serum IGF-I and IGFBP-3 levels. This prompted us to study serum IGF-I and IGFBP-3 concentrations in girls with PT. Thirty-nine girls with premature breast development were studied and classified as PT or CPP according to clinical and laboratory evaluation. Normal prepubertal and pubertal girls were studied as controls. Serum IGF-I and IGFBP-3 were determined in all girls by IRMA. IGF-I levels in PT (155 +/- 61 microg/l) were lower than in CPP (337 +/- 149 microg/l) or late-pubertal controls (355 +/- 84 microg/l) and similar to those found in prepubertal (113 +/- 72 microg/l) and early-pubertal (222 +/- 81 microg/l) girls. Considering the SDS of IGF-I for chronological age (CA), the values observed in PT were in an intermediate position between CPP and prepubertal controls and statistically similar to those observed in CPP and prepubertal girls. IGFBP-3 levels in PT (2.1 +/- 0.5 mg/l) were similar to those found in CPP (2.5 +/- 0.8 mg/l), but only the latter were higher than in prepubertal girls (1.9 +/- 0.9 mg/l). IGF-I/IGFBP-3 molar ratios in PT were in an intermediate position between CPP and prepubertal controls. In conclusion, IGF-I and IGF-I/IGFBP-3 values in PT are intermediate between those observed in prepubertal children and in CPP, suggesting that PT could be a very early stage of puberty with slight but real changes in the GH-IGF axis.     

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目的分析中枢性性早熟(CPP)女童糖脂代谢的特点及脂联素在性早熟女童糖、脂代谢中的作用。方法浙江大学医学院附属儿童医院于2004年6~10月收治50例CPP女童,测量空腹血糖、胰岛素、甘油三酯、胆固醇、脂联素,并做葡萄糖耐量试验和胰岛素释放试验,采用总体胰岛素敏感指数(WBISI)、胰岛素抵抗指数(HOMA-IR)这2个指标来评估胰岛素敏感性和胰岛β细胞功能。并与年龄匹配的正常对照组进行比较。结果(1)CPP女童空腹胰岛素、HOMA-IR明显高于正常对照组(P<0·01)。(2)CPP女童A1组胆固醇较正常对照组明显升高(P<0·05)。(3)CPP女童体重指数(BMI)值均较正常对照组明显升高(P<0·05)。其中超重16%(8/50),肥胖8%(4/50)。(4)CPP女童脂联素均较正常对照组明显下降(P<0·01)。(5)CPP女童BMI值与WBISI显著负相关(r=-0·31,P<0·05),与HOMA-IR显著正相关(r=0·30,P<0·05),与脂联素显著负相关(r=-0·43,P<0·01)。CPP女童脂联素与WBISI显著正相关(r=0·29,P<0·05),多元回归分析显示CPP女童脂联素与WBISI、HOMA-IR无显著相关性。(6)排除12例超重加肥胖CPP女童后再分析显示A1、A2组女童空腹胰岛素、HOMA-IR仍明显高于正常对照组(P<0·01),而脂联素水平3组差异无显著性。结论(1)CPP女童存在不同程度的胰岛素抵抗,尤见于BMI值明显升高的性早熟女童。(2)肥胖或超重的性早熟女童胰岛素抵抗可能与脂联素水平下降有关。     

4岁内儿童性早熟57例

目的探讨4岁内儿童性早熟的病因、诊断要点,研究简易的促性腺激素释放激素(GnRH)激发试验的可行性。方法对57例<4岁性早熟患儿的临床资料进行回顾性分析。57例均行GnRH激发试验,对中枢性与部分中枢性组患儿的LH值进行秩和检验。结果本组男3例,女54例。外周性性早熟36例(63.1%);中枢性性早熟(CPP)4例;部分性CPP17例。CPP促黄体生成素(LH)升高为甚,50%峰值落在60~90min,部分性CPP促卵泡生成素(FSH)升高为甚,84.2%峰值落在90~120 min;CPP与部分性CPP 30、60、90、120 min LH比较有显著差异(P均<0.01)。结论<4岁儿童性早熟以女性发病为主,多为外周性性早熟。GnRH激发试验对病因分类很必需,应在0、60、120 min测LH、FSH,以明确CPP和部分性CPP。     

True precocious puberty in girl. Therapy with LHRH analogs

The authors observed an occurrence of pubertas praecox vera by 42 girls from 8 months to 7 years of age. The purpose of the investigations was to elucidate the possible causes of the precocious symptoms and to estimate the effect of the therapy with various LHRH-analogues. Only in 2 children a cranial tumor was found. In the remaining cases an idiopathic precocious puberty was diagnosed. These children received a therapy with LHRH-analogues: Relefact, Busserelin or Decapeptyl. The authors obtained the best results with the slow releasing Decapeptyl.