Precocious puberty is a common developmental abnormality in the pediatric endocrine system. In order to standardize the diagnosis and treatment of central (true) precocious puberty, the Endocrine Genetics and Metabolism Group of the Pediatrics Section of the Chinese Medical Association has conducted a symposium and formulated the following guidelines for clinical reference. Precocious puberty is a developmental abnormality in which girls present secondary sexual characteristics before the age of 8 years and boys before the age of 9 years. 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 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, and the process of which develops in a progressive manner 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) is routinely injected intravenously at 2.5μg/kg or 100μg/m2, and blood samples are taken at 0min, 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 the synthesized GnRH analog (GnRHa) is stronger than that of the natural one, and the peak value can be diagnosed. effects are stronger than the natural ones, with peaks occurring at 60-120 min, but their use in routine diagnosis is not recommended. Cut-point value of LH peak excitation for diagnosis of CPP: it depends on the gonadotropin assay used, when measured by radioimmunoassay, CPP can be diagnosed when the LH peak is >12.0IU/L in girls, >25.0IU/L in boys, and when the LH peak/FSH peak is >0.6~1.0 (Note: LH peak is the highest value of LH at each point in the excitation test; FSH peak is the highest value of LH at each point in the excitation test; FSH peak is the highest value of LH at each point in the excitation test; FSH peak is the highest value of LH at each point in the excitation test; FSH peak is the peak of LH at each point in the excitation test. FSH peak refers to the highest value of FSH at each time point in the excitation test); when measured by immunochemiluminescence assay (ICMA), LH peak>5.0IU/L, LH peak/FSH peak>0.6 (in both sexes) can diagnose CPP; if the LH peak/FSH peak is>0.3, but <0.6, it should be combined with the clinical close follow-up, repeat the test if necessary, so as not to miss 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 primary diseases. 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 for the treatment of CPP, and the slow-release GnRHa preparations available for children in China are Triptorelin and Leuprorelin; the former is DecapeptyI and the latter is Leuprorelin; the former is DecapeptyI and the latter is DecapeptyI. DecapeptyI the latter for Enantone. GnRHa can effectively inhibit LH secretion, so that the gonadal pause development, sex hormone secretion back to pre-puberty state, thus delaying the growth and fusion of epiphysis, as far as possible to achieve prolonged growth years, improve the final height of adulthood purpose. 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 start of treatment is >11.5 years old for girls and >12 years old for boys. …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 ≥12.5 years for girls and ≥13.5 years for boys; (2) 1 year after menarche for girls or after spermatorrhea for boys. 4. Indications for non-application: (1) When the process of sexual maturation is slow (bone age progression does not exceed age progression) and has little effect on adult height, 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, the initial evaluation of those who believe that no treatment is temporarily required 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: 80-100μg/kg for the first dose, strengthened once after 2 weeks, and then once every 4 weeks (not more than 5 weeks), with a dose of 60-80μg/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), and those with poor inhibition can refer to the first dose, with the maximum amount of 3.75mg/times. In order to know exactly the progress of bone age, clinicians should assess and compare the bone age before and after treatment in person, and should not make judgment based on radiology report only. 2, the monitoring of the treatment: the treatment process every 2 ~ 3 months to check the secondary sexual characteristics and measure height; the first dose of 3 months at the end of the review of the GnRH excitation test, such as LH excitation value in the prepubertal value means that the dose is appropriate; thereafter, the girls only need to regularly review the baseline serum estradiol (E2) concentration or vaginal smears (maturation index), the boys will review the baseline 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 to 12.5 years, at which time it is often difficult to continue to improve height in adulthood if the treatment is prolonged. For those who start treatment at a young age, if their age has caught up with the bone age, and the bone age has reached the normal age of puberty initiation (≥8 years), the predicted height can reach the genetic target height can be discontinued, so that the gonadal axis function restarted, and should be tracked regularly. Monitoring after stopping the drug After the end of treatment, the height, weight and parasympathetic signs recovery as well as the gonadal axis function recovery status should be rechecked every six months. Girls usually present menarche within 2 years after cessation of treatment. Growth deceleration in GnRHa treatment The growth rate in the first six months of GnRHa treatment does not change significantly compared with the pre-treatment period, and after half a year, the growth rate generally falls back to that of pre-pubertal period (about 5 cm/year), and the growth rate in some of the children is <4 cm/year after 1 to 2 years of treatment, and it will be difficult to improve the height in adulthood by continuing the treatment of GnRHa at this time, especially when the bone age is ≥12.0 years old (female) or 13.5 years old (female). females) or 13.5 years (males). Reducing the dose of GnRHa therapy does not improve growth, but risks accelerating bone age. In recent years, the combination of GnRHa and recombinant human growth hormone (rhGH) has been used internationally to overcome growth deceleration. However, it should be noted that in children ≥13.5 years of age (females) or 15 years of age (males), even with the addition of rhGH, the improvement in growth is often not significant because the growth potential of the bone growth plate has been depleted. The use of rhGH should strictly follow the indications for its use, generally only when the child's predicted height in adulthood fails to reach his or her target height; GH should be used in pharmacological therapeutic doses [0.15-0.20 U/(k g thrust)], and side effects should be closely monitored during the process of its application (contraindications to the use of rhGH and monitoring of its side effects during treatment are the same as those of other diseases of growth retardation). For non-idiopathic CPP, concomitant etiological treatment should be emphasized (e.g., surgical treatment of tumors in the saddle region, and concomitant administration of cortisol for congenital adrenocortical hyperplasia combined with CPP). However, in children with hypothalamic malformations and arachnoid cysts, if there are no signs of elevated cranial pressure, then surgery should be postponed and only treated as ICPP. In summary, precocious puberty is a multiaetiologic abnormality of sexual development, and identification of the etiology is critical. The identification of GnRH-dependent precocious puberty should be followed by the exclusion of central organic pathology, especially in boys and those with onset under 6 years of age (both sexes). Idiopathic CPP can be considered as the first choice of GnRHa treatment, but the indications for its application need to be rationalized, and the balance of growth/maturation should be monitored, judged, and mastered during treatment in order to achieve the goal of improving adult height.