Expert citations
- Clinically, according to the etiology and pathogenesis, precocious puberty is usually divided into central precocious puberty (CPP), peripheral precocious puberty (PPP) and partial precocious puberty;
- According to the constitution and syndrome manifestations of children, TCM classifies the syndrome differentiation of precocious puberty in children into three clinical syndrome types: yin deficiency and fire and prosperity pattern, liver depression and fire syndrome, and phlegm and dampness accumulation pattern.
- According to the different types of precocious puberty in children and the severity of disease progression, different Chinese and Western methods can be used to intervene.
- Necessary puberty and precocious puberty science popularization and lifestyle education, and timely and effective psychological intervention are necessary means to prevent and treat psychological and behavioral abnormalities in children with precocious puberty.
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Recently, the Guidelines for the Diagnosis and Treatment of Integrative Traditional Chinese and Western Medicine in Children with Precocious Puberty (2023 Edition) (hereinafter referred to as the "2023 Guidelines") jointly formulated by the Endocrinology Working Group of the Pediatric Professional Committee of the Chinese Association of Integrative Medicine and the Pediatric Professional Committee of the Shanghai Association of Integrative Traditional and Western Medicine were officially released. Compared with the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty (2022) (hereinafter referred to as the "2022 Consensus"), the 2023 version of the guidelines adds relevant content to the TCM diagnosis and treatment of precocious puberty, which integrates the content of Western medicine and TCM diagnosis and treatment of precocious puberty, which is more practical.
In this article, Professor Yu Jian, Chairman of the Pediatric Committee of the Chinese Association of Integrative Medicine and Director of the Department of Traditional Chinese Medicine, Children's Hospital of Fudan University, National Children's Medical Center, is invited to interpret the key points of the 2023 version of the guidelines around the similarities and differences between the 2023 version of the guidelines and the 2022 version of the consensus, in order to further strengthen clinicians' understanding of the 2023 version of the guidelines.
Expert Profile
Prof. Jian Yu
- Clinical Doctor of Integrated Traditional Chinese and Western Medicine, Doctoral Supervisor, Professor, Chief Physician
- Director of the Department of Traditional Chinese Medicine, Children's Hospital of Fudan University
- Director of the Institute of Pediatrics, Institute of Integrated Traditional Chinese and Western Medicine, Fudan University
- Chairman of the Pediatric Professional Committee of the Chinese Association of Integrative Medicine
- Executive Director of the Pediatric Branch of the World Federation of Chinese Medicine
- Chairman of the Pediatric Professional Committee of the Shanghai Association of Integrative Medicine
- He is engaged in the clinical diagnosis and treatment and basic research of pediatric diseases with integrated traditional Chinese and Western medicine, especially in the clinical diagnosis and treatment of pediatric Chinese medicine renal diseases - childhood precocious puberty, menstrual diseases, and kidney diseases
The 2023 version of the guidelines uses the Delphi method to grade the quality of evidence and recommendations in the literature, and the specific criteria are shown in Table 1 and Table 2.
Table 1 Quality of evidence for DELPHI Table 2: Key points of recommendation intensity grading 1: Classification and diagnostic criteria - The consensus of the 2022 version is similar to that of the 2023 version of the guideline "Western medicine classification and diagnostic criteria", and the 2023 version of the guideline adds "pathogenesis and dialectical classification of traditional Chinese medicine"
Clinical classification and diagnostic criteria
Depending on whether the hypothalamic-pituitary-gonadal (HPG) axis function is activated early, precocious puberty is usually clinically divided into central precocious puberty (CPP), peripheral precocious puberty (PPP), and partial precocious puberty (incomplete precocious puberty).
The diagnosis of precocious puberty involves the diagnosis of the cause, type, and degree of development, and requires laboratory aids necessary in addition to a detailed history and physical examination.
The diagnostic criteria for central precocious puberty must meet the following 5 criteria: 1) the onset of secondary sexual characteristics before the age of 7.5 years and the onset of menarche before the age of 10 years in girls, and the onset of secondary sexual characteristics before the age of 9 years in boys. 2) Linear growth accelerates, with an annual growth rate higher than that of normal children. 3) Bone age is advanced, and the bone age exceeds the biological age by 1 year or more. 4) Gonadal development, in girls, pelvic ultrasound showed enlarged uterine and ovarian volumes, and multiple follicles with a diameter of ≥4 mm could be seen in the ovaries, and the testicular volume of boys was ≥ 4 ml. 5) The HPG axis function was activated, and the serum gonadotropin and sex hormone levels reached the level of puberty.
Pathogenesis and syndrome differentiation in traditional Chinese medicine
Pathogenesis of traditional Chinese medicine: Traditional Chinese medicine believes that precocious puberty is located in the "kidney and liver", and kidney yin deficiency and phase fire are the basic pathogenesis of precocious puberty.
TCM syndrome differentiation: Yin deficiency and fire pattern, liver stagnation and fire pattern, and phlegm and dampness syndrome are the three common clinical syndrome types of precocious puberty, but they mostly exist in the form of compound syndrome types, and can generally be diagnosed with 2 or 3 symptoms and signs.
Point 2: Treatment principles and methods
——Both the 2022 consensus and the 2023 version of the guidelines emphasize that "GnRHa treatment is the standard treatment regimen for central precocious puberty", and the 2023 version of the guidelines adds "traditional Chinese medicine treatment for precocious puberty"
Principles and Methods of Western Medicine Treatment
The general principles of treatment are: inhibiting the process of sexual development, delaying the rapid maturation of the epiphysis, improving the lifelong damage caused by advanced bone age, and reducing or avoiding psychological, behavioral, and social problems caused by premature development.
Treatment: GnRHa treatment
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Indications for use:
1) Fast-progressive CPP: the development of skeletal maturation and secondary sexual characteristics was significantly accelerated.
2) Patients with impaired CPP prediction of adult height: predict the 3rd percentile of adult height <, or predict adult height < genetic target height. 3) CPP has psychobehavioral problems directly related to precocious puberty.
4) Rapid progressive puberty bone age progresses rapidly, which can affect the final adult height.
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Treatment Options:
1) 1-month dosage form: the commonly used GnRHa drugs are leuprolide or triptorelin sustained-release agent, the dose is usually 3.75 mg/time, injected once every 4 weeks, and the dose can be reduced for children weighing less than 30 kg, or 1.88 mg/time, injected once every 4 weeks.
2) March dosage form: In recent years, GnRHa drugs have been continuously updated, the types of long-acting preparations have become more abundant, and long-acting inhibitors every 12 weeks (3 months) have also begun to be used in China.
- GnRHa plus growth hormone: if the growth rate decreases (<5 cm/year or 3 months for 3 months<0. 5 cm/month), growth potential is impaired, and the predicted height is less than -2 standard deviation (SD), which is consistent with the indication for growth hormone. Growth hormone may be added to improve height gain after contraindications have been ruled out, but patients require close clinical follow-up. (Level of evidence: II.; level of recommendation C). The combination of GnRHa and growth hormone for more than 12 months was more beneficial for height. Growth hormone can be discontinued when the growth rate is less than 2 cm/year, or when the bone age is > 16 years in boys and 14 years in girls > years.
Principles and methods of TCM treatment
Treatment principle: TCM treatment needs to be combined with syndrome differentiation and disease differentiation, for cases of precocious puberty with non-organic causes, TCM syndrome differentiation can be used alone, if the progress is too fast, and the effect of TCM treatment alone is not ideal, Western medicine or a combination of Chinese and Western medicine can be treated.
TCM syndrome differentiation and treatment: the main clinical treatment is to nourish the kidney, yin and diarrhea and fire, for those who have both liver meridian depression and heat, the liver can be cleared and diarrhea can be cleared, and the phlegm and dampness are supplemented by phlegm and dampness. Syndrome differentiation needs to see the essence through the phenomenon, grasp the core pathogenesis, and distinguish the primary and secondary syndromes, so as to achieve good results.
- Yin deficiency and fire prosperity syndrome treatment: nourish yin and nourish the kidneys, clear and clear the fire. Formula: Zhibodihuang pills plus or minus (Level of evidence: II; level of recommendation: C).
- Liver depression and fire syndrome treatment: soothing the liver and relieving depression, clearing the liver and purging fire. Formula: Dan Yu Xiaoyaosan plus or minus (Level of Evidence: II; Level of Recommendation: C).
- Phlegm and dampness syndrome treatment: strengthen the spleen and dampness, dissolve phlegm and disperse knots. Formula: Erchen decoction plus or minus (level of evidence: II; level of recommendation: C).
Point 3: Treatment evaluation and follow-up
——The 2022 version of the consensus is similar to the 2023 version of the guideline "treatment effectiveness criteria", and the 2023 version of the guideline adds "timing of discontinuation of treatment" and "monitoring and follow-up"
Criteria for treatment response:
- Growth rate is normal or decreased, enlarged breast, uterus, and ovarian tissues in girls retract or do not continue to increase, testicular volume decreases or does not continue to increase in boys, bone age progression is delayed, and the HPG axis is inhibited.
When to discontinue treatment:
- Discontinuation of treatment for idiopathic central precocious puberty should be individualized, and factors such as the child's recent growth rate, satisfaction with predicted height, treatment compliance, quality of life, and the need for sexual development to develop at the same time as those of peers should be considered, not bone age alone.
- The treatment is aimed at improving height, and the course of treatment is longer, and the bone age of girls is more than 12. In boys aged 5 years and older than 14 years, the benefit of treatment in improving height was small.
- For those with partial precocious puberty without obvious bone age and no obvious impairment in predicted height, the drug can be discontinued after the secondary sexual characteristics subside.
Surveillance follow-up:
- Sexual development, height and weight gain, height standard difference score, sex hormone level, uterus and ovaries in girls and testicular volume in boys should be monitored every 3 months, and bone age should be rechecked every 6 months.
- Patients treated with GnRHa should also be observed for local adverse reactions with or without medication.
- Patients with poor response to disease should be carefully evaluated for reasons and treatment should be adjusted.
- For children with a clear diagnosis who have not undergone clinical intervention, it is also recommended that changes in growth rate, sexual development, bone age, etc., should be monitored and evaluated regularly.
- Patients treated with Chinese medicine and proprietary Chinese medicine should have regular follow-up of liver and kidney function and blood and urine routine.
Point 4: The 2023 version of the guideline adds "psychological intervention"
At the same time as puberty is early, some children with precocious puberty will have certain psychological and behavioral abnormalities. Studies have shown that effective treatment of precocious puberty can help alleviate psychological and behavioural abnormalities in children (level of evidence: III; level of recommendation: IV.).
Necessary education and timely and effective psychological intervention are also necessary means to prevent and treat psychological and behavioral abnormalities in children with precocious puberty:
- Explain the causes of precocious puberty and the importance of appropriate treatment to improve the child's prognosis and relieve their concerns.
- Adolescent education and psychological counseling should be done for children, reminding parents to pay attention to cultivating children's awareness of self-protection and preventing the emergence of mental and psychological illness.
- For children with pre-existing psychological and behavioral problems, psychologists will intervene to carry out psychological intervention.
Point 5: The 2023 version of the guideline adds "Diagnosis and Treatment Process of Integrated Traditional Chinese and Western Medicine for Children with Precocious Puberty"
The 2023 version of the guidelines integrates the key content of Western medicine and traditional Chinese medicine diagnosis and treatment of precocious puberty, and is suitable for clinicians of Western medicine, traditional Chinese medicine and integrated Chinese and Western medicine engaged in pediatric clinical work. Figure 1 shows the diagnosis and treatment process of integrated traditional Chinese and Western medicine for children with precocious puberty:
Fig.1 The diagnosis and treatment process of precocious puberty in children with integrated traditional Chinese and Western medicine
Note: CNS, central nervous system, CPP, central precocious puberty, GnRHa, gonadotropin-releasing hormone analogue, GH growth hormone, Tanner stage, stage of sexual development. 【Experts' Conclusion】
The Guidelines for the Diagnosis and Treatment of Precocious Puberty in Children (2023 Edition) fully combines the diagnosis and treatment characteristics of traditional Chinese medicine and Western medicine to introduce the identification, assessment, diagnosis and treatment of precocious puberty in detail, filling the gap in the consensus of integrated traditional Chinese and Western medicine in the diagnosis and treatment of precocious puberty in China. At the same time, compared with the 2022 version of the consensus, the 2023 version of the guidelines has added content related to traditional Chinese medicine and integrated Chinese and Western medicine. In terms of Western medicine treatment, the 2023 version of the guidelines is similar to the 2022 version of the consensus, and unanimously emphasizes that GnRHa is the standard treatment for central precocious puberty. The 2023 version of the guidelines provides clinicians with more comprehensive and feasible guidance for the diagnosis and treatment of precocious puberty, which is expected to further optimize the diagnosis and treatment plan of precocious puberty and improve the level of disease management of precocious puberty in mainland China.
(Guidelines for the Diagnosis and Treatment of Integrative Traditional Chinese and Western Medicine for Children with Precocious Puberty (2023 Edition) co-authored by Yu Jian, Sun Wen, and Sun Yanyan)
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