[Definition] Precocious puberty is a developmental disorder in which secondary sexual characteristics appear before the age of 8 years in girls and 9 years in boys. Central precocious puberty (CPP) is caused by the hypothalamus prematurely increasing the secretion and release of gonadotropin-releasing hormone (GnRH), which prematurely activates the function of the gonadal axis, leading to the development of the gonads and the secretion of sex hormones, resulting in the development of the internal and external genital organs and the presentation of secondary sexual characteristics.CPP is also known as GnRH-dependent precocious puberty, which is a process of progressive development until the development of the reproductive system is mature. [Etiology] 1. Organic lesions of the central nervous system. 2.Peripheral precocious puberty is transformed. Idiopathic CPP (ICPP) without organic lesions. About 80% to 90% of female children have ICPP; on the contrary, more than 80% of male children have ICPP. [Diagnosis] The first step should be to determine whether it is GnRH-dependent precocious puberty, followed by differential diagnosis of the etiology of the disease. I. Diagnostic basis 1. Early appearance of secondary sexual characteristics: before the age of 8 years in girls and before the age of 9 years in boys. 2.Elevated serum gonadotropin level reaches pubertal level. (1) Gonadotropin basal value: If the secondary sexual characteristics have reached the level of mid-puberty, the serum luteinizing hormone (LH) basal value can be used as the initial screening, such as >5.0IU/L, it can be determined that the gonadal axis has been activated, and there is no need to carry out the gonadotropin-releasing hormone (GnRH) stimulation test. (2) GnRH stimulation test: this test is an important diagnostic tool for those who have activated the gonadal axis function and the basal value of gonadotropin is not elevated, GnRH can increase the secretion and release of gonadotropin, and its stimulation peak can be used as a diagnostic basis. GnRH stimulation test method: GnRH (gonadorelin) 2.5 μg/kg or 100 μg/m2 intravenous injection is routinely used, and blood samples are taken at 0min, 30min, 60min, and 90min, and serum LH and follicle-stimulating hormone (FSH) concentrations are measured (the 120min of the classic GnRHa test can be omitted), and the stimulation effect of synthetic GnRH analogues is stronger than that of the natural ones. effects are stronger than the natural ones, with peaks occurring at 60-120 min, but their use in routine diagnosis is not recommended. Cutting value of LH excitation peak for diagnosis of CPP: when measured by immunochemiluminescence assay (ICMA), LH peak >5.0 IU/L, LH peak/FSH peak >0.6 (both sexes) can diagnose CPP; if LH peak/FSH peak >0.3 but <0.6, it should be combined with close clinical follow-up and repeat the test if necessary to avoid missing the diagnosis. 3, gonadal enlargement: girls in ultrasound see ovary volume >1m1, and can see multiple follicles with a diameter of >4mm; boys testicular volume ≥4ml, and with the prolongation of the course of the disease is progressive enlargement. 4. Accelerated linear growth. 5, Bone age beyond the age of 1 year or more. 6.Serum sex hormone level is elevated to pubertal level. Among the above diagnostic bases, 1, 2 and 3 are the most important and necessary. However, if the duration of the disease is very short at the time of consultation, the GnRH stimulation value may overlap with the prepubertal value and not reach the above diagnostic cut-off value; the same is true for the size of the ovaries. These children should be followed for paraphysical progression and accelerated linear growth, and these tests should be reviewed as necessary. In females, linear growth acceleration during puberty usually occurs about half a year to one year after the onset of breast development (B2-B3 stage) and lasts for one to two years; however, there are also cases of delayed onset, and even about 5% of children present one year before menarche or in the year of menarche. In boys, accelerated growth occurs when the testicular volume is about 8-10 ml or one year before the change of voice, and lasts longer than in girls. Advancement of bone age only indicates that sex hormone levels have been increased for a period of time, and is not a specific indicator for the diagnosis of CPP. Children with a short course of the disease and a slow developmental process may not have significant bone age advancement, while peripheral precocious puberty may also have advancement of bone age; elevated levels of sex hormones can not distinguish between central and peripheral precocious puberty. In conclusion, the diagnosis of CPP is comprehensive, and the core problem is that it must be consistent with GnRH dependence, and it is important to follow up the development of sexual characteristics in a progressive manner. The etiological diagnosis should pay attention to collect the medical history related to the etiology of CPP, such as infection, central nervous system lesions and other related symptoms; all children diagnosed with CPP should be excluded from tumors, and need to be examined by MRI or CT of the cranial saddle region. MRI can distinguish hypothalamus and pituitary organ lesions better than CT. Differential diagnosis: Although the GnRH excitation test can largely distinguish central precocious puberty and peripheral precocious puberty, it should be differentiated from GnRH-induced precocious puberty, and should be used for the diagnosis of GnRH-induced precocious puberty. Pure precocious puberty: In partial central precocious puberty (PICPP), FSH is significantly elevated after GnRH provocation (and will be elevated after provocation in normal prepubertal girls), but LH is insignificantly elevated (mostly <5IU/L), and FSH/LH is >1. However, it is worth noting that, in the absence of any clinical precursors, PICPP will be converted to CPP. Therefore, regular follow-up is needed after diagnosis of PICPP, especially for those with recurrent or persistent breast enlargement, and repeat provocation test if necessary. 2, CPP transformed from non-central precocious puberty: such as congenital adrenocortical hyperplasia, McCune-Albright syndrome, etc., we must pay attention to monitoring the occurrence of CPP during the treatment of the primary disease. 3, congenital hypothyroidism accompanied by precocious puberty is a special type of precocious puberty, early in the child’s blood LH basal value is elevated, but not elevated in the GnRH stimulation, the course of the disease is long before the transformation into real CPP. short stature is an important feature. [The treatment of CPP is centered on improving the child’s height in adulthood, and attention should also be paid to preventing psychological problems associated with precocious puberty and early menarche. GnRH analogue (gonadotroping releasing hormone analogue, GnRHa) is generally used in the treatment of CPP, and the slow-release GnRHa preparations available for children in China are Triptorelin and Leuprorelin; the former, such as DecapeptyI Dep and Leuprorelin. DecapeptyI Dep and Diphereline (Dafylline); the latter is Enantone (抑那通). GnRHa can effectively inhibit LH secretion, so that the gonadal pause development, sex hormone secretion back to the state of pre-puberty, thus delaying the growth and fusion of epiphysis, as far as possible to achieve prolonged growth years, improve the final height of adulthood. I. Indications for the application of GnRHa 1. In order to improve the lifelong height in adulthood, the indications for the application of GnRHa are children with significantly impaired growth potential and remaining growth potential, i.e., those whose bone age is significantly ahead of the age of growth and whose epiphyses have not yet begun to merge, the specific recommendations are as follows: (1) Bone age: Bone age ≥ 2 years; girls ≤ 11.5 years old, boys ≤ 12.5 years old. (2) Predicted adult height: girls ≤150 cm, boys ≤160em, or those below their genetic target height minus 2 SD. (3)Bone age/age>1, bone age/height age>1, or height SDS judged by bone age<-2SDS.(4)Rapid sexual development process, bone age growth/age growth>1. 2.Indications for prudent use: the efficacy of improving adult height is poor in the following cases, and should be used with caution, as appropriate: (1)Bone age at the time of initiation of treatment is >11.5 years for girls and >12.5 years for boys; (2)Bone age at the time of initiation of treatment is >11.5 years for girls and >12.5 years for boys; (3)Bone age is >12.5 years for girls, and >12.5 years for boys. 12.5 years of age; (2) genetic target height is 2 standard deviations below the normal reference value (-2SDS). Other causes of short stature should be considered. Indications for contraindication: GnRHa treatment alone is not effective in improving adult height in the following cases: (1) Bone age ≥12.0 years for girls and ≥13.5 years for boys; (2) 1 year after menarche for girls or after spermatorrhea for boys. 4. Indications that do not need to be applied: (1) When the process of sexual maturation is slow (bone age progression does not exceed the age progression) has little effect on height in adulthood, treatment is not required. (2) Bone age is advanced but height growth is rapid, making the height-for-age greater than the bone age and predicting no impairment of height in adulthood. However, because the process of youthful maturation is dynamic, the judgment of each individual should also be dynamic, once the diagnosis of CPP is established, for the initial evaluation of those who do not need treatment for the time being are required to regularly review their height and bone age changes, and regularly reassess the need for treatment, and formulate a treatment plan according to need. Application of GnRHa 1. Dosage: the first dose of 80-100 μg/kg, 2 weeks later, strengthened once, and then once every 4 weeks (not more than 5 weeks), the dose of 60-80 μg/kg, the dose needs to be individualized, according to the inhibition of gonadotropic axis function (including sexual characteristics, sex hormone levels and bone age progression), poor inhibition can be referenced to the first dose, and the maximum amount of 3.75 mg / times. In order to know the exact progress of bone age, clinicians should evaluate and compare the bone age before and after treatment, and should not make judgment only based on the radiology report. 2, monitoring in the treatment: check the secondary sexual characteristics and measure the height every 2-3 months during the treatment; review the GnRH excitation test at the end of 3 months after the first dose, if the LH excitation value is in the pre-pubertal value, then it means that the dose is appropriate; thereafter, the girls only need to review the basal serum estradiol (E2) concentration or vaginal smear (maturation index), and the boys should review the basal level of serum testosterone in order to determine the gonadotropic axis function. In boys, serum testosterone baseline levels are reviewed to determine the status of gonadal axis suppression. Bone age should be rechecked every 6-12 months, and ultrasound of uterus and ovaries should be rechecked at the same time for girls. 3. Treatment: In order to improve height in adulthood, the treatment program of GnRHa usually takes at least 2 years, and it is advisable to stop the treatment for girls at the age of 12.0-12.5 years, at which time it is often difficult to continue to improve height in adulthood if the treatment program is prolonged. For those who start treatment at a young age, if their age has caught up with their bone age, and their bone age has reached the normal age of puberty initiation (≥8 years old), and the predicted height can reach the genetic target height, the drug can be discontinued, so as to allow their gonadotropic axis function to restart, and they should be followed up on a regular basis.