Violations of puberty are detected in 3-5% of girls. A significant role in the development of the disease is played by hereditary predisposition, as well as adverse factors (radiation, hypoxia, viral infections, some drugs). Anomalies of the reproductive system are more common in children born to patients with alcoholism, drug addiction, endocrine diseases, as well as from elderly parents.
Sexual development is a genetically programmed process that begins at the age of 7–8 years and ends at the age of 17–18 years. The appearance of secondary sexual characteristics and menstrual discharge up to 7 years should be regarded as premature sexual development (CPD). Underdevelopment or lack of secondary sexual characteristics in 15-16 years is attributed to delayed sexual development.
Premature sexual development can be isosexual, i.e. on the female type, and heterosexual – on the male type. An IPR of the isosexual type can have a positive (true PPR), constitutional and ovarian (false PPR) form.
The cerebral form is considered a true CPD, because the hypophysotropic zones of the hypothalamus are involved in the pathological process, where the premature secretion of GnRH leads to the production of gonadotropins in the pituitary gland, which in turn stimulates the secretion of estrogen in the ovaries. The defeat of the central nervous system in girls with PPR may be functional or organic. The causes of functional disorders are the impact of unfavorable factors during the period of prenatal development, maternal diseases, complicated labor, infectious diseases, and intoxications suffered in the first years of life. Organic damage to the central nervous system is usually the result of asphyxiation, birth trauma, cerebral infection (meningitis, encephalitis, other neuroinfections). There are less common brain tumors – ganglioneuroma, hamartomas, astrocytomas.
The constitutional form of IDP is not accompanied by any cerebral or neurological pathology. The sequence of the appearance of secondary sexual characteristics is not disturbed, and the duration of puberty is similar to the physiological one. It is only the age of menarche that matters (8–9 years).
With PPR of ovarian genesis caused by a hormone-producing tumor, there is no neurological symptoms, secondary sexual characteristics are slightly developed. The sequence of the appearance of signs of puberty is changed: acyclic menstrual-like discharge appears first. Somatic development is not accelerated. Clinical manifestations of PPR with follicular cysts consist in scant serum secretions from the genital tract and a slight increase in the mammary glands. In follicular cysts, PPR symptoms are transient and undergo a reverse development as the follicular cyst regresses.
In MacKun-Albright-Brytsev syndrome, both incomplete and complete forms of CPD are possible. In girls with incomplete form, physical development is accelerated. The growth rate of the tubular bones and the rate of ossification of their epiphyses are the same, so they are no different from healthy ones in constitution and height. With the full form of sexual development significantly accelerated, characterized by acyclic uterine bleeding.
Diagnostics. The diagnosis of PPR is established on the basis of anamnesis, the dynamics of sexual and physical development, gynecological examination. Ultrasound of the pelvic organs, determination of the level of gonadotropins and estrogens in the blood are required, laparoscopy is performed if necessary, and bone age is determined and neurophysiological methods are used (reo- and electroencephalography – respectively REG, EEG). If a pituitary tumor is suspected, an MRI is indicated. Endocrinologists, neurologists, and ophthalmologists should be involved in the examination of these patients.
Treatment. CPD therapy includes treatment of the underlying disease that caused CPD, and inhibition of CPD. When CPD cerebral genesis treatment is carried out by neurologists or neurosurgeons. To inhibit puberty, drugs are used that act on hypothalamic structures that regulate the synthesis of lyuliberin or block hormones on target organs (triptorelin – decapeptyl depot4, diferelin4). Children with a constitutional form of IDD need only dynamic observation. Ovarian tumors should be removed, followed by histological examination. After 1.5-2 months after the operation in these patients, all signs of PPR are regressed. Follicular cysts should not be removed immediately, since cysts with a diameter of no more than 3–4 cm undergo a reverse development within 2–3 months, and the signs of arrhythmias disappear.
Heterosexual PPD is associated with hyperproduction of androgens and is observed in congenital dysfunction of the adrenal cortex (ADKN), adrenogenital syndrome (AGS), or virilizing adrenal tumors. The simple viril form of AGS is a genetically determined congenital disease associated with the deficiency of the C21 hydroxylase enzyme system in the adrenal cortex. This defect leads to a lack of cortisol formation and an increase in the release of ACTT. Increased stimulation of the latter causes an increase in the synthesis of androgens and bilateral hyperplasia of the adrenal cortex. Adrenal dysfunction begins in utero, almost simultaneously with the beginning of their functioning as an endocrine gland.
Clinical symptoms. In a child immediately after birth, an abnormal structure of the external genital organs is noted: the clitoris is hypertrophied (even penislike), the large labia merge resemble the scrotum, the vagina and the urethra open on the perineum with a single opening of the urogenital sinus. With severe virilization, sex determination is difficult. However, the ovaries and uterus of these children are developed correctly, the chromosome set 46, XX (false female hermaphroditism).
In children with AHS, growth in the first 10 years of life is dramatically accelerated, but by 10 years it slows down due to the rapid completion of the processes of ossification. The constitution acquires dysplastic features: broad shoulders, narrow pelvis, short limbs, long body. Under the influence of an excess of androgens, viril hypertrichosis begins and progresses, and the timbre of the voice decreases. The mammary glands do not develop, menstruation is absent.
Diagnostics. The most informative diagnostic signs of AGS are a sharp increase in the excretion of 17-CU and a high level of cortisol precursor in the blood – 17-hydroxyprogesterone.
Treatment. Therapy begins with the time of diagnosis and consists in the long-term use of glucocorticosteroids. The dose depends on the age, body weight and severity of hyperandrogenism. Early treatment allows to normalize sexual development, to achieve regular menstruation during ovulatory cycles, and further provides pregnancy and childbirth.
Feminizing plastics of virilized genital organs in girls with congenital dysfunction of the adrenal cortex are recommended to be carried out in one stage until the age of sexual self-identification (up to 3 years). Surgical treatment consists of resection of the cavernous bodies of the clitoris simultaneously with the reconstruction of the vagina. Delayed sexual development (CRA) may have cerebral, constitutional, and Ovarian forms.
Causes of central nervous system DSS can be injuries, infections, intoxication, mental and nervous disorders, stress. The manifestation of cerebral ZPR can be anorexia nervosa, i.e. refusal of food. In such patients, the level of gonadotropins in the blood sharply decreases, while the potential ability of the pituitary gland to secrete gonadotropins is maintained. The constitutional form of the CRA, like the CPD, is hereditary.
The ovarian form of CRA is extremely rare and is accompanied, as a rule, by a decrease in the follicular apparatus. Such ovaries are called hypoplastic or insensitive, resistant to gonadotropic stimulation. It is possible that transferred infections and intoxications play a role in the pathogenesis of this pathology.
Clinical symptoms. Patients with ZPR differ from their peers by the insufficient development of secondary sexual characteristics and the absence of menstruation. Build eunuchal: tall, long arms and legs with a short torso. Bone age corresponds to the passport or slightly behind him. Gynecological examination noted hypoplasia of the external and internal genitalia. Drastic weight loss leads to cessation of menstruation; if menarche is not yet present, primary amenorrhea is observed.
CRA is not always a manifestation of any pathology. Thus, the constitutional form has a hereditary, familial character. In these girls, menarche occurs at the age of 15-16 years, but later on menstrual and reproductive functions are not impaired.
Diagnostics. Examination of the CRA aimed at establishing the level of damage to the reproductive system. Of great importance are the anamnesis, physique and the development of secondary sexual characteristics. If a central center of genesis is suspected, a non-echological examination (EEG, REG, Echo EG) is necessary. MRI of the brain, ultrasound scan of the pelvic organs, determination of the level of hormones in the blood, x-rays of the hands, densitometry, as well as laparoscopy with ovarian biopsy and karyotyping are used as additional methods.