I. Examination
1.Basic sex hormone measurement
Basal luteinizing hormone (LH) has screening significance, such as LH <0.1 IU/L indicates no central puberty initiation, while LH>3.0-5.0 IU/L can confirm central puberty initiation (stimulation test is required if the diagnosis cannot be confirmed by the basal value). β-HCG and alpha-fetoprotein (AFP) should be included in the basic screening, which is an important clue for the diagnosis of HCG-secreting germ cell tumor. Elevated estrogen and testosterone levels are diagnostic adjuncts.
2.Gonadotropin-releasing hormone (GnRH) stimulation test (important basis for confirming the diagnosis of central precocious puberty)
(1) Method: Gonalin 2.5μg/kg (maximum dose 100μg) is injected intravenously, and serum LH and follicle stimulating hormone (FSH) levels are measured before and 30, 60 and 90min after injection.
(2) Judgment: Chemiluminescence measurement, such as peak excitation LH>3.3-5.0 IU/L is the judgment of true developmental boundary, while LH/FSH ratio>0.6 can be diagnosed as central precocious puberty. Currently, it is considered that a single excitation value of 30-60 min after excitation, meeting the above criteria, can also be diagnosed.
If the peak excitation is dominated by elevated FSH and low LH/FSH ratio, it may be early stage of simple premature breast development or central precocious puberty, and the latter requires regular follow-up and rechecking of excitation test when necessary.
3.Uterine ovary ultrasound
Unilateral ovarian volume ≥1-3 ml and multiple follicles ≥4 mm in diameter (newborns also have follicles, the key is to look at the size of the follicles, follicles over 4 mm in diameter are developing follicles), the ovaries can be considered to have entered pubertal development; uterine length >3.4-4 cm or uterine volume >2.5 ml can be considered to have entered pubertal development, endometrial shadow is visible suggesting estrogen is meaningfully elevated. The endometrial shadow indicates a meaningful increase in estrogen.
4.Bone age
It is an important basis for predicting adult height. Bone age is crucial to determine whether menstruation is early and to predict whether adult height is short, and is also an important clinical reference to determine whether a child with precocious puberty needs injection intervention.
5.Cranial pituitary MRI
A cranial MRI (focusing on the pituitary gland in the saddle area) is required after the diagnosis of central precocious puberty (CPP), especially in the following cases.
(1) All boys with a confirmed diagnosis of precocious puberty.
(2) Girls with onset under 6 years of age.
(3) Those with rapid sexual maturation process or other manifestations of central pathology (e.g., headache, dizziness, blurred vision, etc.).
6. Screening for other etiologies
Further endocrine examinations should be conducted according to specific clinical features and after the initial screening of endocrine hormones, such as thyroid function examination to exclude hypothyroidism induced precocious puberty; imaging examinations of gonads, adrenal glands or other related organs should be done as needed, for example, more than 2/3 of boys with precocious puberty can often find the cause, and in addition to the above examinations, ultrasound examinations of testes, adrenal glands, abdominal cavity and other organs should be performed to exclude tumors, etc.
II. Treatment
Not all patients with precocious puberty need treatment!
The indications that do not need treatment are
(1) Those with slow sexual maturation (bone age progression does not exceed age progression) and no significant effect on adult height.
(2) Although the bone age is advanced, but the height growth rate is also fast, and the predicted adult height is not impaired. Because pubertal development is a dynamic process, the above indicators need to be dynamically observed for each individual. For those who do not need treatment for the time being, regular review and evaluation are needed to adjust the treatment plan.
GnRH analogs (GnRHa) are the main treatment options, and currently the most commonly used formulations are the extended-release formulations of treprostinil and leuprolide.