What Are the Different Types of Precocious Puberty Treatment?

Precocious puberty is a common developmental abnormality in the pediatric endocrine system, which refers to the abnormality of the development of secondary sexual characteristics in girls before the age of 8 and boys before the age of 9. Central precocious puberty (CPP) is caused by the hypothalamus increasing the secretion and release of gonadotropin-releasing hormone (GnRH) in advance, activating the function of the gonad axis in advance, leading to the development of gonads and secretion of sex hormones, which makes internal and external genital development and Bisexuality is presented. CPP is also known as GnRH-dependent precocious puberty, and its process develops progressively until the reproductive system matures.

Basic Information

nickname: Precocious puberty
English name
English alias: premature puberty
Visiting department: Pediatrics, Endocrinology

Multiple groups: Girls before 8 years old, boys before 9 years old
Common causes: Related to central nervous system organic lesions, idiopathic CPP, etc.
Common symptoms: Girls before the age of 8 and boys before the age of 9 have enlarged gonadal and secondary sexual characteristics

Causes of childhood precocious puberty

1. Central nervous system organic lesions.

2. The transformation of peripheral precocious puberty.

3. Idiopathic CPP (ICPP) has no organic lesions. 80% to 90% of female children are ICPP; male children are the opposite, more than 80% are organic. It is speculated that this part of precocious puberty is closely related to the stimulation of environmental endocrine disruptors.

Clinical manifestations of precocious puberty in children

Women show breast development, enlargement of the labia minora, estrogen-dependent changes in vaginal mucosal cells, enlargement of the uterus and ovary, appearance of pubic hair, and menarche. In men, testis and penis enlarge, pubic hair appears, muscles are developed, and voices become thicker. Both men and women have accelerated growth and accelerated bone maturation, which can ultimately lead to life-long heights below target heights. With central nervous system diseases such as intracranial tumors, there may be headache, vomiting, vision changes, or other neurological symptoms and signs.

Precocious puberty test

Imaging examination

(1) X-ray examination of the wrist bones to check the bone age.

(2) Ultrasound B girls showed ovarian volume> 1ml and multiple follicles> 4mm in diameter. Boys had testicular volume 4ml, which increased progressively with the course of the disease.

2. Laboratory inspection

Blood was taken to measure FSH, LH, E2 and testosterone. The LH / FSH ratio is small in the early stage, increased in the middle stage, increased LH secretion, increased LH / FSH, increased E2 greater than 10 pg / ml, and women can also measure increased testosterone in bleeding. Testosterone in men's blood can reach 50 to 100 pg / ml.

3.GnRH excitation test

GnRH or similar excitement tests can be performed if necessary.

Diagnosis of precocious puberty in children

Should first determine whether it is GnRH-dependent precocious puberty.

1. Second sexual characteristics appear early

Girls are 8 years old and boys are 9 years old.

2. Serum gonadotropin levels rise up to adolescent levels.

(1) Basal value of gonadotropin If the secondary sexual characteristics have reached the level of mid-puberty, the basal value of serum luteinizing hormone (LH) can be used as a preliminary screening, such as> 5.0IU / L, it can be determined that the gonad axis has been activated It is no longer necessary to perform a gonadotropin-releasing hormone (GnRH) challenge test.

(2) GnRH challenge test This test is an important diagnostic method for those whose gonad axis function has been started and the gonadotropin base value is not increased. GnRH can increase the release of gonadotropin secretion, and its peak stimulation can be used as a diagnostic basis.

Cut-poit value for the diagnosis of the LH excitation peak of CPP: LH peak> 5.0IU / L, LH peak / FSH peak> O.6 can diagnose CPP; such as LH bee / FSH peak> O.3, but <0 At 6 o'clock, close clinical follow-up should be combined, and the test should be repeated if necessary to avoid missed diagnosis.

3. Gonad enlargement

Under B-mode ultrasound, girls saw ovarian volume> 1ml and multiple follicles with diameter> 4mm. Boys had testicular volume 4ml, which increased progressively with the course of the disease.

4. The linear growth of height is accelerated.

5. Bone age is over 1 year or more.

6. Serum sex hormone levels rise to adolescent levels.

Among the above diagnostic criteria, 1, 2, and 3 are the most important and necessary. However, if the course of disease at the time of consultation is very short, the GnRH excitation value may overlap with the prepubertal value and cannot reach the above-mentioned diagnostic cut value; the same is true for ovarian size. Such children should be followed up for the progression of parasexual characteristics and the acceleration of linear growth, and should be repeated if necessary.

Check the above tests. The linear acceleration of puberty in female children generally appears 6 to 12 months after the onset of breast development and lasts for 1 to 2 years; however, there are also late cases, and even about 5% of children show up 1 year before or at the time of menarche. . Accelerated growth of boys occurs when the testicular volume is 8-10ml or one year before the voice changes, and the duration is longer than that of girls. Advancement of bone age only indicates that the level of sex hormones has been elevated for a period of time, and is not a specific indicator for the diagnosis of CPP. Children with short course and slow development may not have significant bone age, and peripheral precocious puberty may also have bone age. High cannot distinguish between central and peripheral precocious puberty. In summary, the diagnosis of CPP is comprehensive, and the core problem is that it must be GnRH-dependent, and clinical follow-up development of progressive signs is of great significance.

Attention should be paid to collecting medical history related to the etiology of CPP, such as infection, central nervous system disease and other related symptoms; tumors should be excluded for all children diagnosed with CPP, and an MRI examination of the skull saddle area should be performed. MRI has better resolution of hypothalamus and pituitary organic lesions than CT.

Differential diagnosis of precocious puberty in children

Although the GnRH challenge test can generally distinguish between central precocious puberty and peripheral precocious puberty, the following should be identified:

Simple premature breast development

That is, part of central precocious puberty (PICPP), FSH significantly increased after GnRH challenge (normal prepubertal girls also increase after challenge), but LH did not increase significantly (most L), and FSH / LH> 1. But it is worth noting that in the absence of any clinical aura, PICPP will be converted to CPP. Therefore, regular follow-up is needed after diagnosis of PICPP, especially for those with repeated breast enlargement or persistent regression, and repeated challenge tests if necessary.

2.CPP transformed from non-central precocious puberty

Such as congenital adrenal hyperplasia, McCune-Albright syndrome, etc., we must pay attention to monitoring the occurrence of CPP during the treatment of the primary disease.

3. Precocious puberty associated with congenital hypothyroidism

It is a special type of precocious puberty. The blood LH value of early children increases, but it does not increase after GnRH stimulation, and it turns into true CPP after a long course of disease. Short stature is an important feature.

Precocious puberty in children

Drug treatment

The purpose of CPP treatment is to improve the height of children in adulthood. Attention should also be paid to preventing psychological problems caused by precocity and early menarche. GnRH analogs (GnRHa) are commonly used to treat CPP. At present, domestic sustained-release GnRHa preparations for children include triptorelin and leuprolide acetate.

GnRHa can effectively inhibit the secretion of LH, suspend the development of gonads, and return the secretion of sex hormones to the prepubertal state, thereby delaying the growth and fusion of the epiphysis, as far as possible to extend the growth period and improve the final adult height.

(1) Indications for the application of GnRHa 1) In order to improve the lifetime height in adulthood, the applicable indications are children with significantly impaired growth potential and residual growth potential, that is, those who have significantly advanced bone age and have not yet started to fuse at the metatarsus. Specific suggestions are as follows: bone age 2 years old; girls 11.5 years old, boys 12.5 years old. It is predicted that the height of adult girl <150 cm, boy age> 1, bone age / height age> l, or height SDS age increase based on bone age> 1. 2) Indications for caution The effect of improving adult height is poor. It should be used with caution when: bone age girls> 11.5 years and boys> 12.5 years at the beginning of treatment. If the genetic target height is 2 standard deviations below the normal reference value, other reasons for short stature should be considered. 3) Inappropriate indications GnRHa alone is not effective in improving adult height in the following cases: bone age girls 12.5 years old, boys 13.5 years old; girls after menarche or 1 year after spermogenesis. 4) Indications that do not need to be applied People with slow sexual maturity (the progression of bone age does not exceed the progression of age) have little effect on adult height and do not need treatment. Although the bone age is advanced, the height growth speed is fast, making the height age greater than the bone age, and it is predicted that the adult height will not be damaged. However, the process of maturity is dynamic. The judgment of each individual should also be dynamic. Once the CPP diagnosis is established, those who do not need treatment for the initial evaluation need to regularly review their height and bone age changes, periodically re-evaluate the need for treatment, and develop treatment plans as needed.

(2) Application method of GnRHa 1) The first dose of 80 100g / kg, strengthen once every 2 weeks, and then every 4 weeks (not more than 5 weeks), the dose is 60 80g / kg, the dose needs to be individualized, according to Inhibition of gonadal axis function (including sexual characteristics, sex hormone levels, and bone age progression), those with poor inhibition can refer to the first dose. In order to understand the progress of bone age accurately, clinicians should personally evaluate and compare the bone age before and after treatment, and it is not appropriate to make judgments based on radiology reports alone. 2) Monitoring during treatment Check the second sexual characteristics and measure height every 2 to 3 months during the treatment; review the GnRH challenge test at the end of 3 months for the first dose. If the LH challenge value is in the prepubertal value, it means that the dose is appropriate; Girls only need to regularly check the basal serum estradiol (E :) concentration or vaginal smear (maturity index), while boys need to check the serum testosterone basal level to determine the inhibition of gonad axis function. The bone age was reviewed every 6 to 12 months, and the girls were also examined for uterine and ovarian B ultrasound. 3) Course of treatment In order to improve adult height, GnRHa usually takes at least 2 years. Girls should stop treatment when the bone age is 12.0 ~ 12.5. At this time, it is often difficult to continue to improve adult height if the treatment is extended. For those who start treatment at a younger age, if their age has caught up with the bone age, and the bone age has reached the normal adolescent initiation age (8 years), the drug can be discontinued when the height can reach the genetic target height, so that the gonad axis function is restarted. It should be tracked regularly.

(3) Monitoring after discontinuation

After the end of treatment, the status of height, weight and recovery of parasexuality and function of gonad axis should be reviewed every six months. Girls usually have menarche within 2 years after stopping treatment.

(4) Treatment of growth deceleration in GnRHa treatment

The growth rate of GnRHa during the first half of treatment is not significantly different from that before treatment. After half a year, the growth rate generally declines to the prepubertal growth rate (about 5cm / year). Some children have a growth rate of <4cm / year after 1 to 2 years of treatment. When GnRHa continues to be treated, it will be difficult to improve its adult height, especially when bone age is 12.0 years (female) or 13.5 years (male). Reducing the GnRHa treatment dose does not improve growth, but instead risks increasing bone age. In recent years, GnRHa and recombinant human growth hormone (rhGH) have been used to overcome the growth deceleration. However, it should be noted that for children with bone age 13.5 years (female) or 15 years (male), the bone growth plate The growth potential has been exhausted, and even with the addition of rhGH, the improvement in growth is often not significant. The use of rhGH should strictly follow the application indications, and it is generally only used when the predicted adult height of the child cannot reach its target height; GH should be treated with pharmacological treatment [0.15 0.20U / (kg · d)]. Monitor side effects closely (contraindications to rhGH use and monitoring of side effects during treatment are the same as for other stunting disorders).

2. Etiology treatment

For non-idiopathic CPP, the etiology treatment should be emphasized at the same time (such as the surgical treatment of tumors in the saddle area, and congenital adrenal hyperplasia combined with CPP should be given cortisol at the same time). However, in children with hypothalamic hamartomas and arachnoid cysts, surgery is postponed if there is no evidence of increased intracranial pressure and only treated by ICPP.

To sum up, precocious puberty is a multi-cause sexual developmental abnormality, and the identification of the cause is very important. GnRH-dependent precocious puberty should be ruled out after central organopathy, especially in boys and those under 6 years of age (both sexes). Idiopathic CPP may be considered the first choice of GnRHa treatment, but the application indications need to be reasonably grasped. During the treatment, the growth / maturity balance should be monitored, judged and mastered to achieve the purpose of improving adult height. In the process of treatment, care should be taken to avoid contact with substances with estrogen effects, light diet, exercise, and avoid obesity.