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.     

Central precocious puberty in girls: prediction of the etiology]

Precocious puberty (PP) is defined in girls by the occurrence of pubertal development before the age of 8. This development raises 3 questions: 1) Is it abnormal puberty or variant of the normal? 2) If abnormal puberty, is it of central, hypothalamic-pituitary, or peripheral, ovarian or adrenal origin? 3) If central, is it idiopathic or due to a lesion, and is there indication to treat it? The PP in a girl with no previous medical history is usually of central and idiopathic origin. However, isolated central PP may reveal a CNS lesion, particularly an optic glioma with its risk of blindness. Two independent predictors of CNS lesion are the age at PP onset of less than 6 years old, and increased plasma estradiol concentration. The selection of the girls for neuroradiological imaging should be based on these two parameters. However, neuroradiological imaging remains necessary until the prospective confirmation of their predictive value.     

Intellectual function of girls with precocious puberty

The IQ of 52 girls with precocious puberty (mean age 9.5 +/- 2.8 years) was compared with that of 51 normal matched control subjects (mean age 9.7 +/- 2.8 years) and with that of eight girls with fast puberty (onset at normal age but accelerated advancement). Girls with precocious puberty had a significantly higher verbal IQ score than the control subjects but no difference was found in the performance score. The distribution of the verbal IQ score in the girls with precocious puberty was skewed toward the upper side of the theoretical distribution curve. The distribution was two or more times the expected theoretical percentile in the above average area (greater than 110, 56.9% v 25%), and five times more in the very superior area (greater than 130, 10.1% v 2.2%). The girls with fast puberty had the same behavior as the population with normal development. The results are interpreted as possible evidence of an effect of sex hormones on brain development, especially on the left hemisphere, during the prepubertal period.     

Rathke's cleft cyst in two girls with precocious puberty

Rathke's cleft cysts arise from remnants of Rathke's pouch and are usually found incidentally on MRI or autopsy. In childhood, the most common presenting symptoms of Rathke's cleft cysts are endocrine abnormalities, such as reduced growth hormone secretion, hyperprolactinemia, or diabetes insipidus. Non-specific symptoms, such as headache and visual disturbance, may also occur. Although precocious puberty has occasionally been described in association with suprasellar lesions, such as hamartomas, arachnoid cysts, and craniopharyngiomas, to our knowledge there have been no documented cases secondary to Rathke's cleft cysts. We report here two patients, both of whom presented with precocious puberty, and were found to have Rathke's cleft cysts.     

Early growth acceleration in girls with idiopathic precocious puberty

OBJECTIVE: To determine the growth pattern of girls with idiopathic precocious puberty (IPP) from birth until diagnosis. STUDY DESIGN: We studied 47 girls with IPP and 35 control girls. In each subject, height and weight were measured at diagnosis, whereas data on height from birth until diagnosis were taken from the personal health book of the patient. Height standard deviation score (HSDS) and body mass index SDS were calculated. RESULTS: Mean age (+/-SD) of the girls with IPP was 7.6 (1.1) years and of control girls was 7.5 (0.9) years. At birth, HSDS of the patients with IPP was -0.01 (0.8); at the age of 2 years, 0.42 (1.2); at the age of 4 years, 0.64 (1.1); and at diagnosis, 1.23 (1.7) (P < .001). HSDS of control girls was 0.02 (0.8) at birth, 0.25 (0.8) at 2 years, 0.12 (0.9) at 4 years, and 0.19 (1.1) at assessment (P > .05). There was no statistical difference between body mass index SDS of the patients 0.6 (1.1) versus that of control girls 0.5 (1.0). CONCLUSIONS: The early growth acceleration pattern may be used as an additional clue to the diagnosis of idiopathic precocious puberty.     

Central precocious puberty in 48,XXYY Klinefelter syndrome variant

We report the first case of central precocious puberty in a patient with 48,XXYY Klinefelter syndrome variant. We also report clinical characteristics, growth pattern, endocrine data and pathological testicular findings. The patient did not receive medical care for his precocious pubertal development, because of adequate height prognosis, and reached normal height for both his target height and Klinefelter patients. Since precocious puberty seems to occur in Klinefelter syndrome and its variants, we advise karyotype analysis in boys with mental retardation, gynecomastia, small testes and precocious onset of puberty.     

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。     

Central precocious puberty and growth hormone deficiency in a boy with Prader-Willi syndrome

In Prader-Willi syndrome (PWS) hypothalamic dysfunction is the cause of hormonal disturbances, such as growth hormone deficiency (GHD), hypogonadism, and delayed or incomplete puberty. Only a few cases of central precocious puberty (CPP) have been reported. We describe an 8.8-year-old PWS boy, with microdeletion of chromosome 15q, who developed CPP. On admission, height was 131.1 cm (+0.17 SD), BMI 26.2 kg/m², pubic hair (Ph) 2, and testis 4.5 ml. We found increased growth velocity (7 cm/year), high testosterone levels, pubertal response to GnRH test, and advanced bone age (10.6 years). An evaluation of growth hormone (GH) secretion revealed a deficiency. Pituitary MRI was normal. LHRH analogue therapy (Leuproreline 3.75 mg/28 days i.m.) was started at 8.9 years and discontinued at 11.3 years, when the patient had bone age of 13 years. During therapy, growth velocity, testosterone, FSH, and LH peak decreased significantly, with no pubertal progression. Growth hormone therapy (0.24 mg/kg/week) was started at 9.5 years and discontinued at 15.3 years because the patient had bone age of 17 years. After interrupting LHRH therapy the patient demonstrated spontaneous pubertal progression with pubertal gonadotropin and testosterone. At 16.3 years, height was 170 cm (−0.48 SDS), BMI 36.3 kg/m², Ph 4, testis volume 10 ml and there was a combined hypothalamic and peripheral hypogonadism hormonal pattern (normal LH even with low testosterone and undetectable inhibin B with high FSH). To our knowledge this is the fourth male patient with genetically-confirmed PWS demonstrating CPP and GHD and the first with a long follow-up to young adulthood.     

Behavior problems and social competence in girls with true precocious puberty

We report a controlled standardized behavioral assessment of 33 girls with true precocious puberty using the Child Behavior Checklist. Although a majority of the girls were reported not to have behavior problems, many were reported to have a dysphoric adjustment to their condition. Twenty-seven percent of the girls with true precocious puberty scored greater than 2 SD above the mean on the Total Behavior Problem scale 10 times the expected prevalence rate. They also scored significantly higher (P less than 0.01) than matched controls on both the internalizing or "overcontrolled symptom" and externalizing or "undercontrolled symptom" scales. Forty-eight percent scored greater than 2 SD above the mean on the Social Withdrawal scale. The high prevalence of reported problem behaviors in this sample may be related directly or indirectly to the precocious maturation mediated by biologic, psychologic, social, and environmental variables. Although elevated levels of sex steroids may directly contribute to increased aggressive and hyperactive behaviors, they may also be modified by social and environmental factors.     

Preserving adult height potential in girls with idiopathic true precocious puberty

We designed a prospective study of height potential in girls with idiopathic precocious puberty, comparing the presenting features of girls with and without evidence of reduced adult height potential. The 14 girls with impaired adult height prognoses (group 1) were reexamined after treatment with a gonadotropin releasing hormone agonist, nafarelin. The seven girls with the prognosis of unimpaired height (group 2) were followed without therapy. We found that the group could be distinguished at initial examination by the greater bone age/height age ratio of group 1 (mean +/- SEM: 1.4 +/- 0.06 vs 1.0 +/- 0.05; p less than 0.005) and by the greater difference between predicted height and target height in group 1. The mean predicted height in group 1 was significantly less than the mean target height (150.7 +/- 2.1 vs 165.4 +/- 3.0 cm; p less than 0.005), whereas the mean predicted and target heights in group 2 were similar (165.4 +/- 3.0 vs 164.3 +/- 2.1 cm). Initial estradiol levels were also greater in group 1 than in group 2 (21.6 vs 10.6 pg/ml; p less than 0.05), although this difference was not sustained during follow-up. In group 1, nafarelin therapy suppressed the pituitary-gonadal axis, and although there was a transient reduction in height potential in girls with the youngest bone ages during the first 6 months of therapy, 2 years of treatment slightly improved predicted heights from 150.7 +/- 2.1 to 152.7 +/- 2.0 cm (p less than 0.05). Height predictions also increased without therapy during the 2-year observation period in group 2, from 165.4 +/- 3.0 to 168.7 +/- 4.1 cm (p less than 0.05). Our data indicate that gonadotropin releasing hormone agonist therapy preserves height potential in girls with an initially impaired height prognosis, and that height potential is preserved without therapy in those with a good initial height prognosis.