Delayed puberty in children

Delay in puberty is the absence of an increase in mammary glands in girls who have reached the age of 13, or the development of secondary sexual characteristics beyond the upper limit of the age standard by 2.5 standard deviations. As a delay in puberty, the absence of menarche to 15.5-16 years of a girl's life, stopping the development of secondary sexual characteristics for more than 18 months, delay of menarche for 5 years or more after the timely onset of the growth of the mammary glands are also estimated. It should be noted that the appearance of sexual embryology (pubic and axillary) should not be considered a sign of puberty.

ICD-10 code

• E30.0 Delay in puberty.
• E30.9 Disorder of puberty, unspecified.
• E45 Delay in puberty due to protein-energy deficiency.
• Е23.0 Hypopituitarism (hypogonadotropic hypogonadism, isolated gonadotropin deficiency, Callman's syndrome, panhypopituitarism, pituitary cachexia, pituitary insufficiency of BDU).
• E23.1 Medication hypopituitarism.
• E23.3 Dysfunction of the hypothalamus, not elsewhere classified.
• E89.3 Hypopituitarism arising after medical procedures.
• E89.4 Ovarian failure that occurs after medical procedures.
• N91.0 Primary amenorrhea (violation of menstruation in the puberty period).
• E28.3 Primary ovarian failure (low estrogen, stable ovarian syndrome).
• Q50.0 Congenital absence of ovaries (except Turner syndrome).
• E34.5 Syndrome of testicular feminization, androgen resistance syndrome.
• Q56.0 Hermaphroditism, not elsewhere classified (the sex gland containing the tissue components of the ovary and testicle, is ovotestis).
• Q87.1 Syndromes of congenital anomalies, manifested mainly by dwarfism (Russell's syndrome).
• Q96 Turner Syndrome and its variants.
• Q96.0 Karyotype 45.XO.
• Q96.1 Karyotype 46.X iso (Xq).
• Q96.0 Karyotype 46.X with an abnormal sex chromosome, with the exception of iso (Xq).
• Q96.3 Mosaicism 45.X / 46.XX or XY.
• Q96.4 Mosaicism 45, X / another cell line (s) with an abnormal sex chromosome.
• Q96.8 Other variants of Turner syndrome.
• Q97 Other sex chromosome abnormalities and female phenotype, not elsewhere classified (including a woman with a karyotype of 46.XY).
• Q99.0 Mosaic (chimera) 46XX / 46XY, the true hermaphrodite.
• Q99.1 46XX-true hermaphrodite (with bar-gonads, 46XY with bar-gonads, pure gonadal dysgenesis - Svayer syndrome).

Epidemiology

Among the white population, about 2-3% of girls at the age of 12 and 0.4% of girls at the age of 13 have no signs of puberty. The main reason for delay in puberty is gonadal insufficiency (48.5%), hypothalamic insufficiency (29%), enzymatic defect of hormone synthesis (15%), isolated deficiency of anterior pituitary (4%), pituitary tumors (0.5% ), of which 85% are prolactinomas. The incidence of gonadal dysgenesis with a karyotype of 46.XY (Svayer syndrome) is 1 per 100,000 newborn girls.

Screening

In the context of neonatal screening, the definition of sexual chromatin in all newborns (laboratory confirmation of the sex of the child). Monitoring of the dynamics of growth is necessary in girls with signs of congenital syndromes for the timely correction of the rates of puberty.

Against the background of treatment of delayed puberty, it is necessary to determine the annual dynamics of girls' growth, their puberty, bone age, the level of gonadotropins (LH and FSH) and estradiol in venous blood.

Classification of delayed puberty

Currently, taking into account the level of damage to the reproductive system, three forms of delay in puberty are distinguished.

The constitutional form of delay in puberty is expressed in the delay in the increase in mammary glands and in the absence of menarche in a somatically healthy girl at the age of 13 years who has an equal physical lag (length and body weight) and biological (bone age) development.

Hypogonadotropic hypogonadism is a delay in puberty caused by a pronounced deficiency in the synthesis of gonadotropic hormones due to aplasia or hypoplasia, damage, hereditary, sporadic or functional insufficiency of the hypothalamus and pituitary gland.

Hypergonadotropic hypogonadism is a delay in puberty caused by congenital or acquired lack of secretion of hormones of sexual glands. Congenital forms represent the dysgenesis or agenesis of the ovaries or testicles. There are two forms of ovarian dysgenesis: typical - Turner syndrome (in our country, the Shereshevsky-Turner syndrome) and "clean" in the karyotype of 46.XX; and three forms of dysgenesis of testicles: typical (45.XO / 46.XY), "pure" (Svayer syndrome) and mixed, or asymmetric. In a typical form, the patients notice multiple stigmata of embryogenesis, characteristic of Turner's syndrome. "Pure form" is characterized by ribbon-like gonads in the absence of somatic abnormalities of development. The mixed form is distinguished by the asymmetry of development of internal sexual glands (undifferentiated sternum on one side and testicle or tumor with the opposite one, absence of gonad on one side and tumor, sternum or testicle with opposite). However, in recent years, the division of XY-dysgenesis (with the exception of Turner's syndrome) into a complete and incomplete form (complete and partial gonadal dysgenesis) is increasingly encountered in foreign literature. This approach emphasizes the fact that all types of dysgenesis of sexual glands represent different links of the same pathogenetic mechanism of sexual differentiation disorder. Thus, this pathology is considered as one disease, that is, various variants of 46, XU-gonadal dysgenesis.

Causes and pathogenesis of delayed puberty

Constitutional form

The constitutional delay of puberty, as a rule, is hereditary. The formation of this syndrome is caused by etiological factors leading to late activation of the hypothalamic-pituitary function and suppressing the impulse secretion of the hypothalamic GnRH). The pathogenetic mechanisms of their effects remain unclear. Numerous studies have been devoted to the study of monoamine control of the hypothalamic-pituitary function in children with delayed puberty. There was a general trend in the level of catecholamines: a reduction in the levels of noradrenaline and epinephrine and an increase in serotonin concentration. Another putative reason for the delay of pubertal is functional hyperprolactinemia, which may be associated with a decrease in dopaminergic tone, which leads to a decrease in the impulse secretion of both gonadotropic hormones and growth hormone.

Delay in puberty in hypogonadotropic hypogonadism (central genesis)

The delay in puberty with hypogonadotropic hypogonadism is based on a deficiency of gonadotropin hormone secretion as a result of congenital or acquired CNS disorders.

Causes and pathogenesis of delayed puberty

Symptoms of delayed puberty

The main signs of delayed puberty in girls on the background of hypofunction of the central parts of the reproductive system regulation (central form of puberty delay):

• absence or underdevelopment of secondary sexual characteristics at the age of 13-14;
• absence of menstruation at the age of 15-16 years;
• hypoplasia of the external and internal genital organs in combination with growth retardation.

The combination of these signs of hypoestrogenism with severe body weight deficit, decreased vision, impaired thermoregulation, prolonged headaches or other manifestations of neurological pathology may indicate a violation of the central regulatory mechanisms.

Symptoms of delayed puberty

Diagnosis of delay in puberty

Find out the presence of stigma of hereditary and congenital syndromes and peculiarities of puberty of both parents and immediate relatives (I and II degree of kinship). Family history should be collected during the conversation with the patient's relatives, primarily with the mother. Assess the characteristics of intrauterine development, the period of the newborn, the growth rate and psychosomatic development; find out the living conditions and features of nutrition of the girl from the moment of birth, data on physical, psychological and emotional loads; specify the age and nature of operations, the course and treatment of diseases carried over the years of life. Particular attention should be paid to information about the presence of infertility and endocrine diseases in relatives. As well as infectious and somatic diseases in the child in the first year of life, CNS diseases, craniocerebral trauma, since the presence of these conditions and diseases in girls significantly increases the likelihood of an unfavorable prognosis of restoration of the function of the reproductive system. Most girls with a family form of delayed puberty have a history of menarche from their mother and other close relatives and delayed and delayed sexual pilosis or development of the external genitalia in the fathers. In patients with Callman's syndrome, the presence of relatives with a reduced sense of smell or complete anosmia should be clarified.

Diagnosis of delay in puberty

Treatment of delayed puberty

• Prevention of malignancy of dysgenetic gonads located in the abdominal cavity.
• Stimulation of pubertal growth growth in patients with growth retardation.
• Replenishment of the deficiency of female sex hormones.
• Stimulation and maintenance of the development of secondary sexual characteristics for the formation of a female figure.
• Activation of the processes of osteosynthesis.
• Prevention of possible acute and chronic psychological and social problems.
• Prevention of infertility and preparation for procreation through extracorporeal fertilization of the donor egg and embryo transfer.

Treatment of delayed puberty

Forecast

The prognosis of fertility in patients with a constitutional form of delayed puberty is favorable.

With hypogonadotropic hypogonadism and ineffective therapy consisting of individually selected antihomotoxic drugs or drugs that improve the function of the central nervous system, fertility can be temporarily restored by exogenous administration of LH and FSH analogues (with secondary hypogonadism) and GnRH analogs in the cirrchoral regimen (with tertiary hypogonadism).

Prevention

Data confirming the existence of the developed measures to prevent the delay of puberty in girls are absent. When central forms of the disease, due to nutritional deficiency or inadequate physical exertion, it is advisable to observe the work and rest regime against the background of rational nutrition before the onset of puberty. In families with constitutional forms of delayed puberty, it is necessary to observe the endocrinologist and gynecologist from childhood. With dysgenesis of gonads and testicles, prevention does not exist.

[1], [2], [3], [4], [5]