(I) Pathogenesis According to the causative factors. Precocious childhood breast hypertrophy can be divided into 2 categories: primary precocious breast hypertrophy and secondary precocious breast hypertrophy. 1, primary precocious breast hypertrophy, also known as true precocious breast hypertrophy or somatic precocious breast hypertrophy. No organic cause can be found in the clinic. The normal secretion function of the hypothalamus-pituitary-ovary axis is established early before puberty as in normal sexual maturity. It has been found that the secretion of sex hormones is often significantly increased in these children. For example, estrogen, androgens and 17-corticosterone. Androgens and 17-corticosterone urinary excretion. The urinary excretion of estrogen, androgens and 17-corticosterone all reach the level of normal adults. And this type of children can have normal development and normal delivery without other abnormal findings. Novak believes that primary precocious breast hypertrophy may be more common than secondary precocious breast hypertrophy, and also reported six cases of primary precocious breast hypertrophy. No ovarian tumors were detected on microscopic examination. Adrenal and pituitary tumors or other lesions. 2.Secondary precocious breast hypertrophy Because the breast enlargement of children is not based on the “hypothalamus-pituitary-ovarian axis” secretion function maturity advancement. Instead, it is secondary to other diseases. Therefore, it is also called pseudo-precocious breast hypertrophy. The causes are related to the following diseases. (1) Organic damage to the central nervous system: such as encephalitis. Tuberculous meningitis. Head injury. Congenital cerebral hypoplasia. Microcephaly. Hydrocephalus. Hypothalamus. Ventricular malformation tumor of the third ventricle, etc. (2) Adrenocortical hyperplasia or tumor: the adrenal glands secrete a variety of hormones. Females have estrogen and progesterone. When adrenal hyperplasia or tumor. The secretion of these hormones will increase. It can stimulate breast development in girls. (3) Primary hypothyroidism: It is a primary thyroid insufficiency, not a pituitary hypothyroid hormone secretion. When the thyroid gland is hypothyroid, the pituitary gland increases the secretion of thyrotropin under negative feedback regulation, which also causes the secretion of gonadotropin and prolactin to increase, resulting in precocious puberty. (4) Functional ovarian tumor: about 10%. Granulosa cell – follicular membrane cell tumor is common. Ovarian teratoma is the second most common. All of them can cause precocious puberty. These tumors can secrete a lot of estrogen. They cause breast development and vaginal bleeding. (B) Pathogenesis 1, pathogenesis Primary precocious breast hypertrophy is due to the child’s physical factors. The normal secretion function of “hypothalamus-pituitary-ovarian axis” has been established before puberty. The early secretion of gonadotropin releasing hormone causes the anterior pituitary gland to secrete follicular maturation hormone and luteinizing hormone, which stimulates the early development of ovarian follicles and the secretion of estrogen, thus causing the development and maturation of the mammary glands and reproductive tract. Therefore, these children may have normal development and normal delivery. In secondary precocious breast hypertrophy, endogenous or exogenous hormones stimulate the corresponding organs prematurely and excessively due to various diseases, resulting in the development of secondary sexual characteristics and sex organs. For example, organic lesions of the central nervous system directly stimulate or destroy the neural structures that inhibit the gonadotropic center of the child, so that the hypothalamus, pituitary gland secretion function is advanced. Because of the undeveloped gonads, these children do not have ovulation and fertility, although they have enlarged breasts and vaginal bleeding. (1) Gross morphology: the mammary glands are obviously enlarged. The texture is soft. The epidermis is unchanged. In some cases, a disk shape is visible under the nipple. The texture is soft and hard. (2) Histomorphology: microscopic examination reveals that the enlarged breast is mostly composed of fat cells and fibrous tissue. There are a few mammary glands in the center. What are the manifestations of precocious puberty and how to diagnose? 1, primary precocious breast hypertrophy The appearance of female precocious secondary sexual characteristics include breast development, vulva development, the appearance of pubic hair and axillary hair, the onset of menstruation and so on. Breast development can be divided into 5 stages. (1) Mammary gland development: the characteristics of breast development are similar to normal pubertal breast development. The nipple and areola are colored, and a disc-shaped nodular breast tissue can be touched under the areola, with medium quality, clear boundary, smooth surface, activity, and no adhesion with the skin. There is tenderness of the lump under the areola. The degree of breast enlargement varied from 1 to 2 cm to 7 to 8 cm in diameter. With breast development and enlargement. The subareolar mass gradually shrinks. Disappearance. Breasts can be adult size (Figure 1). (2) The appearance of secondary sexual characteristics: in addition to breast development. The vulva tends to mature, with the appearance of pubic hair, and the internal genitalia and vagina also mature in advance. The most prominent of these is the early activity of ovarian function. There is follicular maturation and ovulation, the first menstrual period occurs earlier, and conception and childbirth are possible. (3) Rapid growth in height: as in normal puberty. The body grows suddenly. Skeletal development is higher than that of girls of the same age. (4) Blood gonadotropin levels are not age-appropriate but consistent with developmental stage. Urinary 17-ketosteroids are increased, but consistent with bone age. 2.Secondary precocious breast hypertrophy Although there are some precocious manifestations, the gonads are undeveloped and the hypothalamic-pituitary function measurements are consistent with age. (1) Functional ovarian tumor: except for the development of breasts and other secondary sexual characteristics and (or) menstruation, the child may be completely asymptomatic. They may also have abdominal distension, abdominal pain and palpable masses in the abdomen or pelvis. Vaginal bleeding usually occurs before the development of secondary sexual characteristics, which is one of the clinical features of these patients. (2) Central nervous system lesions: when the lesions are small, precocious puberty is the only symptom. It is easy to be misdiagnosed as primary precocious breast hypertrophy. Dynamic observation is needed, and the history of brain diseases can be asked. Such as hydrocephalus, meningitis, mental retardation. Certain brain tumors can present with hypothalamic dysfunction after a period of time. Such as uremia, obesity or other psychiatric symptoms. When the intracranial pressure increases and compresses the optic nerve, visual impairment and visual field defects can also occur. (3) Primary hypothyroidism: Most of them show delayed development of secondary sexual characteristics. A few may have precocious puberty, breast development, lactation, vaginal bleeding, increased blood LH and FSH, but slow response to LH-RH. Serum estrogen is several times that of adults. Pituitary hyperplasia is seen on cranial radiography or CT. Symptoms of precocious puberty may disappear after thyroxine supplementation. (4) multiple bone fibrous developmental anomalies: there is no familial tendency, and its clinical features are: ① one side of the bone tissue fibrous osteitis; ② non augmentation of brown pigmentation of the skin, mostly occurring on the affected side; ③ endocrine disorders. Vaginal bleeding occurs at the early stage of sexual development, and the values of LH and FSH in blood are increased. To the pituitary hormone-releasing hormone (LH-RH) is true precocious puberty response, some patients serum LH and FSH is not high. It does not respond to LH-RH.X-ray examination reveals areas of osteopenia in the long bones of the extremities. Pseudocysts are formed. Pathologic fractures may occur. Areas of density thickening are also common at the base of the skull. (5) Exogenous hormone intake: There is a history of misuse of estrogen drugs or frequent use of Chinese herbal tonic. The E2 content in the blood is very high, up to more than 340pg/ml. There are breast enlargement, nipple, areola coloring, leukorrhea increase or vaginal bleeding, but naturally subside and return to normal after stopping the drug. The appearance of secondary sexual characteristics and the onset of menstruation in girls between the ages of 8 and 12 is considered precocious puberty. If there is also breast enlargement, the diagnosis of precocious puberty can be confirmed. In order to achieve etiologic diagnosis, it is often necessary to distinguish between primary and secondary breast hypertrophy, i.e., when making the diagnosis of primary precocious breast hypertrophy, it is necessary to exclude secondary precocious breast hypertrophy due to diseases of the ovaries, adrenal glands, pituitary gland, thyroid gland and central nervous system. Its diagnosis and differential diagnosis points are as follows: 1, detailed medical history, carefully ask whether there is a history of trauma and surgery; whether there is a history of high fever, convulsions, epilepsy, the development of sexual characteristics, vaginal bleeding; whether there is any misuse of estrogen-containing medications or health care products. General physical examination including height, weight, sitting height. General nutritional status and health condition, neurological examination, fundus and visual field examination. Intelligence test, etc. Development of secondary sex characteristics, pelvic examination except ovarian tumor. 3.Laboratory examination and imaging examination exclude thyroid function abnormality, ovarian tumor, adrenal tumor. Intracranial space-occupying lesions and multiple bone fibrous developmental abnormalities. How should precocious childhood breast hypertrophy be treated? (A) Treatment The purpose of treatment for precocious gynecomastia is to inhibit menstruation and the development of the second sexual characteristic. 1, primary precocious gynecomastia treatment (1) sexual knowledge education: the child should be educated about sexual knowledge and menstrual hygiene, to lift the inferiority complex, sense of shame and other psychological changes. Tell the child that this disease is a precocious disease with a good prognosis. (2) Drug treatment: ① Methylhydroxyprogesterone (Amphetamine): a high-efficiency progesterone, can inhibit the secretion of pituitary gonadotropin, causing amenorrhea, breast atrophy. Decreased ovarian function is seen on vaginal smear cytology. Intramuscular injection method: intramuscular injection of long-acting medroxyprogesterone 150-200mg every 10-17 days; oral method: medroxyprogesterone tablets. 10-30mg/d (4mg per tablet). The treatment plan is made according to the severity of its condition and whether the symptoms are controlled. Menstruation usually stops after treatment. Breast reduction. ② Megestrol acetate (megestrol): 6～8mg/day, to be taken orally in 2 divided doses until the secondary sexual characteristics subside. Laboratory tests are obviously improved. Gradually reduce to 4mg/d. Take orally in 2 doses. Gonadotropin-releasing hormone analogs (GRH-A): these drugs have a therapeutic effect on primary precocious puberty by inhibiting the release of pituitary gonadotropins through the reverse regulation of the receptors. Buserelin is commonly used. 2-3 times/d. 100mg each time. administered by nasal inhalation. Continuous application for half a year to 2 years. 2, secondary precocious breast hypertrophy treatment should be based on the cause of its different treatment methods. (1) Precocious puberty caused by central nervous system disease, such as tumor can be surgically removed. (2) Ovarian granulosa cell and blast cell tumors, etc., can be surgically removed and treated with chemotherapy or radiation therapy. (3) Pituitary gland,. Adrenocortical hyperplasia or tumor-induced precocious breast hypertrophy. The primary tumor can be removed. (4) Hypothyroidism can be supplemented with thyroxine and so on. (5) Simple development of breast: regular follow-up. Surgery is not suitable and blind biopsy is contraindicated.