Adrenogenital syndrome: treatment, forms, tests and diagnostics. Adrenogenital syndrome

Hormones, some of which are produced in the adrenal glands, are responsible for primary and secondary sexual characteristics. There is a congenital disease characterized by dysfunction of these glands internal secretion and excessive secretion of androgens. An excess of male sex hormones in the body leads to significant changes in the structure of the body.

Adrenogenital syndrome - causes

The pathology under consideration arises as a result of a congenital genetic mutation that is inherited. It is rarely diagnosed, the incidence of adrenogenital syndrome is 1 case in 5000-6500. Change genetic code provokes an increase in the size and deterioration of the adrenal cortex. The production of special enzymes that are involved in the production of cortisol and aldosterone is reduced. Their deficiency leads to an increase in the concentration of male sex hormones.

Adrenogenital syndrome - classification

Depending on the degree of growth of the adrenal cortex and the severity of symptoms, the described disease exists in several variations. Forms of adrenogenital syndrome:

• salt-losing;
• virilny (simple);
• post-pubertal (non-classical, atypical).

Adrenogenital syndrome - salt-wasting form

The most common type of pathology that is diagnosed in newborns or children of the first year of life. In the salt-losing form of adrenogenital syndrome, a violation is characteristic hormonal balance and insufficiency of the function of the adrenal cortex. This type of disease is accompanied by too low aldosterone concentration. It is necessary to maintain the water-salt balance in the body. Specified adrenogenital syndrome provokes a violation of cardiac activity and jumps in blood pressure. This occurs against the background of the accumulation of salts in the kidneys.

Adrenogenital syndrome - viril form

A simple or classic variant of the course of the pathology is not accompanied by the phenomena of adrenal insufficiency. The described adrenogenital syndrome (AGS of the viril form) leads only to changes in the external genital organs. This type of disease is also diagnosed at an early age or immediately after childbirth. Internally, the reproductive system remains normal.

The type of disease under consideration is also called atypical, acquired and non-classical. This adrenogenital syndrome occurs only in women who are sexually active. The cause of the development of pathology can be both a congenital mutation of genes, and. This disease often accompanied by infertility, therefore, without adequate therapy, adrenogenital syndrome and pregnancy are incompatible concepts. Even with successful conception the risk of miscarriage is high, the fetus dies even in the early stages (7-10 weeks).

Adrenogenital syndrome - symptoms

The clinical picture of the described genetic anomaly corresponds to the age and form of the disease. Adrenogenital syndrome in newborns can sometimes not be determined, which is why the sex of the baby may be incorrectly identified. Specific signs of pathology become noticeable from 2-4 years old, in some cases it manifests itself later, in adolescence or maturity.

Adrenogenital syndrome in boys

With the salt-losing form of the disease, symptoms of a violation of the water-salt balance are observed:

• diarrhea;
• severe vomiting;
• low blood pressure;
• convulsions;
• tachycardia;
• weight loss.

Simple adrenogenital syndrome in male children has the following symptoms:

• enlarged penis;
• excessive pigmentation of the skin of the scrotum;
• dark epidermis around the anus.

Newborn boys are rarely given this diagnosis, because the clinical picture at an early age is mild. Later (from the age of 2) adrenogenital syndrome is more noticeable:

• hair growth on the body, including the genitals;
• low, rough voice;
• (acne vulgaris);
• masculinization;
• acceleration of bone formation;
• short stature.

It is easier to determine the disease in question in female infants, it is accompanied by the following symptoms:

• hypertrophied clitoris, outwardly very similar to a penis;
• large labia, look like a scrotum;
• the vagina and urethra are combined into the urogenital sinus.

Against the background of the presented signs, newborn girls are sometimes mistaken for boys and brought up in accordance with an incorrectly established sex. Because of this, at school or adolescence these children often have psychological problems. Inside, the girl's reproductive system is fully consistent with the female genotype, which is why she feels like a woman. The child begins internal contradictions and difficulties with adaptation in society.

After 2 years, congenital adrenogenital syndrome is characterized by the following features:

• premature growth of pubic and armpit hair;
• short legs and arms;
• muscularity;
• the appearance of facial hair (by the age of 8);
• male physique (broad shoulders, narrow pelvis);
• lack of growth of mammary glands;
• short stature and massive body;
• rough voice;
• acne disease;
• late onset of menstruation (not earlier than 15-16 years);
• unstable cycle, frequent delays in menstruation;
• or oligomenorrhea;
• infertility;
• jumps in blood pressure;
• excessive pigmentation of the epidermis.

Adrenogenital syndrome - diagnosis

To identify hyperplasia and dysfunction of the adrenal cortex help instrumental and laboratory research. To diagnose adrenogenital congenital syndrome in infants, a thorough examination of the genitals and computed tomography (or ultrasound) is performed. Hardware examination allows you to detect the ovaries and uterus in girls with male genital organs.

To confirm the alleged diagnosis, a laboratory test for adrenogenital syndrome is carried out. It includes the study of urine and blood for the content of hormones:

• 17-OH-progesterone;
• aldosterone;
• cortisol;
• 17-ketosteroids.

Additionally assigned:

• clinical blood test;
• general urinalysis.

Treatment of adrenogenital syndrome

Get rid of the considered genetic pathology impossible, but its clinical manifestations can be eliminated. Adrenogenital syndrome - clinical recommendations:

1. Lifelong use of hormonal drugs. To normalize the functioning of the adrenal cortex and control the endocrine balance, you will have to constantly drink glucocorticoids. The preferred option is Dexamethasone. The dosage is calculated individually and ranges from 0.05 to 0.25 mg per day. In the salt-wasting form of the disease, it is important to take mineralcorticoids to maintain the water-salt balance.
2. Appearance correction. For patients with the described diagnosis, vaginal plastic surgery, clitorectomy and other surgical interventions are recommended to ensure that the genitals are given correct form and the appropriate size.
3. Regular consultations with a psychologist (on request). Some patients need help in social adaptation and acceptance of themselves as a full-fledged person.
4. Stimulation of ovulation. Women who want to get pregnant need to take a course of special medications that provide adjustment menstrual cycle and suppression of androgen production. Glucocorticoids are taken throughout the gestation period.

Adrenogenital syndrome (AGS) is characterized by a dysfunction of the adrenal cortex, the basis of which is the inferiority of the enzyme systems that ensure the production of cortisol. The lack of glucocorticoids reduces their inhibitory effect on ACTH according to the principle feedback, the level of the latter increases and as a result, hyperplasia of the adrenal cortex develops with increased production and release of androgens (testosterone, dehydroepiandrosterone and androstenediol). The frequency of pathology is 1 per 3000-6000 births.

AGS is genetically determined congenital disease. According to the nature of the violation of enzyme processes in the adrenal glands, there are five forms of the syndrome:

Deficiency of the enzyme 21-hydroxylase leads to a partial disruption of the processes of 21-hydroxylation, which contributes to increased secretion of androgens by the adrenal glands and the appearance of virilization (virile form);

21-hydroxylation defect - almost total absence 21-hydroxylase disrupts the synthesis of 17?-hydroxyprogesterone, hydrocortisone and aldosterone, which causes not only virilization, but also contributes to the loss of salts and the development of signs of addisonism (salt-losing form);

With a lack of 11 α-hydroxylase, a defect in 11 α-hydroxylation is formed, which leads to over-education mineralocorticoids (DOCs) and retention of sodium and water in the body, and all this, in addition to virilization, causes hypertension (hypertensive form);

The lack of 3-oxidehydrogenase disrupts the processes of steroidogenesis with the development of acute adrenal insufficiency and with a defect in the synthesis of steroids from cholesterol (a rare lipid form of AGS);

The form of AGS, in which there is high fever, due to high levels of etiocholanolone (rare hyperthermic form).

Depending on the period of exposure to androgens, AGS is divided into the following forms: antenatal (congenital), prepubertal and postpubertal. At the same time, it has been established that the relative defect of 21-hydroxylation progresses with age and causes an increase in the activity of the adrenal glands in the biosynthesis of androgens. This not only explains the pathogenesis of post-pubertal AGS, but also indicates the unity of the genesis of pre- and post-pubertal forms of the disease. Since biochemical disorders in the adrenal glands in congenital and postpubertal AGS are qualitatively the same, diseases such as female pseudohermaphroditism, premature puberty with virilization (according to the heterosexual type), as well as AGS in the post-pubertal period, should be considered as diseases with a common genesis, differing only in the severity of enzymatic disorders in the adrenal glands and the time of their manifestation. Despite these enzyme disorders in different forms according to the clinical picture and the time of manifestation of AGS, patients often have normal production of cortisone and excretion of hydrocortisone, which is due to increased activity of the adrenal cortex under the stimulating effect of ACTH, which is not able to eliminate even high levels of androgens.

Congenital AGS (a simple virilizing form of adrenal cortex dysfunction) is characterized by virilization of the genital organs (enlargement of the clitoris, the appearance of the urogenital sinus), manifested in utero. Pregnancy and childbirth in mothers proceed normally, and physical and psychomotor development in children also occurs without any special features. In newborns, features in the structure of the external genital organs are revealed: hypertrophied or penis-shaped clitoris, deepening of the vestibule of the vagina, urogenital sinus, high perineum, underdevelopment of the small and large labia. In children with ACS, there is an acceleration of growth rates in the first decade (2 times compared to healthy ones). At 12-15 years old, body growth is 5 times less than in healthy girls. This is due to the acceleration of the processes of growth and ossification due to hormonal disorders. Sometimes at 13-14 years of age, growth stops, not reaching the average. Structural changes are detected bone tissue(gross trabecular, broad-boned structure). There is excessive bone formation due to endosteal and peristal osteogenesis, in connection with which the bone beams and the cortical layer of the bone thicken. All this testifies to the predominance of osteogenesis processes over bone resorption, while normally they proceed in parallel. The physique of girls has a dysplastic appearance: broad shoulders, narrow pelvis, short limbs with massive tubular bones. Puberty begins at 6-7 years of age and proceeds according to the heterosexual type: male secondary sexual characteristics develop, the clitoris increases, a low timbre of voice is noted, an increase in cricoid cartilage and muscle strength. Mammary glands and menstrual function are absent. The growth of the uterus is slowed down and its size at 16-18 years is much less than normal. Colpocytologically, up to 50% of intermediate cells are detected, which indicates estrogenic influences. The level of gonadotropins in age aspect elevated. Along with the acceleration of somatic development, cerebral structures are also activated, as evidenced by the earlier formation of frequency and rhythm. electrical activity brain. All this is done under the influence of increased levels of androgens. At the same time, when a basal level of hormones is provided in the ovaries, cyclic maturation of follicles and ovulation are absent. Patients have positive sex chromatin and a female karyotype (46 XX), which distinguishes AGS from a virilizing tumor of the adrenal cortex and other forms of hermaphroditism. In hormonal studies, there is an increase in the excretion of 17-ketosteroids by 6-8 times (at 4-6 years old up to 64 mmol / day at a rate of up to 8 mmol / day) and at 16-18 years old (175-200 mmol / day and 24-28 mmol/day, respectively), which decreases to 50% during the prednisolone test.

The salt-wasting form of AGS is characterized by the fact that in children in the first days or during the first year of life, along with pseudohermaphroditism, mineral metabolism is disturbed. This is manifested by anxiety, poor appetite, weight loss or delayed weight gain, vomiting, dehydration and hypoglycemia. This form AGS is caused by a profound deficiency of the enzymes C21-hydroxylase and pronounced violation hydroxylation processes. In this case, there is an insufficiency of adrenal function with a decrease in aldosterone excretion and normal production of cortisol or a decrease in the latter with an increase in the level of progesterone and 17-deoxycortisone. Against the background of these hormonal changes, hypoglycemia, hyperkalemia with dehydration and hypotension occur.

A more rare, hypertensive form of AGS develops as a result of a defect in the C21-hydroxylase enzyme with a violation of the synthesis of cortisol, corticosterone and aldesterone with an excess of 11-deoxycortisol, 17-ketosteroids and deoxycorticosterone. Against this background, virilization and hypertension develop. Other forms (lipid, hyperthermic) are very rare.

Adrenogenital syndrome in pre- and puberty characterized by premature puberty with signs of virilization, i.e. postnatal form of the disease. By the first menarche, male secondary sexual characteristics appear. Patients have short stature (150-155 cm), thick short limbs and a narrow pelvis. Menstruation is absent, mammary glands are undeveloped. The uterus and ovaries are small. Sex chromatin within normal limits, female karyotype (46 XX). Diagnosis of this form of AGS is not difficult.

It is difficult to diagnose the so-called erased form of AGS. Virile symptoms with her appear before or immediately after menarche, which comes on time or with some delay. Then develops hypomenstrual syndrome or amenorrhea. With the advent of hirsutism, the mammary glands decrease in size. With low growth in patients, virilization of the figure is noted. In connection with hyperandrogenism, the closure of bone growth zones is accelerated and body growth stops prematurely. The reproductive organs are developed female type, sometimes with some clitoral hypertrophy and reduced uterine size. In the adrenal glands, an increased (1.5-2 times) content of androgens is produced and enough estrogen compounds. AT differential diagnosis importance has a test with dexamethasone or ACTH, which reduce the excretion of 17-CS by 50% (and do not affect it in adrenal tumors). After the test with ACTH, the excretion of 17-CS in AGS increases by 2-3 times. With the help of ultrasound, the organs of the small pelvis are determined, radiographically - the state of the skeletal system.

The post-pubertal (simple virilizing) form of AGS develops with a small defect in C21-hydroxylase of the adrenal glands and is clinically manifested during puberty from 12-15 years of age. In childhood, the girl grows and develops normally. The disease is manifested by a genetically induced enzyme deficiency of steroidogenesis. Menarche occurs on time (at 11-13 years), hypomenstrual syndrome immediately manifests itself, then amenorrhea develops. Androgenic body type is formed. There is underdevelopment of the mammary glands, slight hypertrophy of the clitoris and hypoplasia of the uterus. The ovaries are somewhat enlarged and soft in texture. Hormonal changes are characterized by increased excretion of 17-KS, levels of androsterone, DEA and testosterone. The number of estrogenic compounds is increased due to less active fractions (estrone, estriol). Hyperprolactinemia is often detected.

A simple virilizing form of AGS in childbearing period(Apert-Galle syndrome) is also caused by a congenital, but incomplete defect in the adrenal enzyme system. Characterized by virilization varying degrees with the appearance of secondary male sexual characteristics (hirsutism, coarsening of the voice, clitoral hypertrophy) and defeminization (hypomenstrual syndrome or amenorrhea, atrophy of the mammary glands, reduction of the uterus and ovaries, disappearance of subcutaneous fatty tissue, leveling of the roundness of body contours). Often, only one symptom can be expressed - hirsutism. There is a latent corticoid insufficiency: decreased performance, headaches, hypotension. Metabolic disorders are characterized by obesity, hyperglycemia with glucosuria, or the development diabetes(Usher-Thirs syndrome). Patients become aggressive, with neuropsychiatric disorders ( depressive states) and severe vegetative-vascular symptoms. The disease often manifests itself after stressful situations, infections, injuries, i.e. after conditions that cause maximum tension of the adrenal cortex. The study noted a decrease in the level of cortisone, excretion of metabolites, corticosteroids, genital steroid hormones and an increase in androgens.

The constitutional (idiopathic) form of hirsutism can manifest itself in pubertal or post-pubertal periods. It is believed that the disease is more common in brunettes than in blondes, as well as in women of the oriental type, in general, in 10-5% of women. Other than hirsutism, none pathological symptoms no. These are actually healthy women with a higher predisposition to any violations (breakdowns) of menstrual and generative functions. They mark increased content adrenal testosterone. Hirsutism explained hypersensitivity follicles to androgens, even with their normal content. More often the disease manifests itself according to the laws of heredity.

Differential diagnosis should be carried out separately for each form of AGS. The diagnosis is determined by clinical data, the results of hormonal functional research, ultrasound, laparoscopy and other auxiliary methods. The diagnosis of congenital adrenal hyperplasia is based on clitoral hypertrophy with various other vulvar anomalies followed by progressive virilization after birth. With the salt-wasting form of congenital AGS, patients die early in life from pylorospasm or pneumonia. early form prepubertal AGS is confirmed by heterosexual (with signs of virilization) precocious puberty. But at the same time there are no violations from the external genitalia. The accelerated appearance of ossification points is characteristic. Late AGS in the postpubertal period is differentiated with tumors of the adrenal glands and the syndrome of late scleropolycystic ovaries. In both diseases, there is an increase in the ovaries, but in AGS they are always smaller and softer than in PCOS, when they are large, dense with a whitish shell. Functional hormonal tests with ACTH, with hCG and dexamethasone (according to 17-KS excretion) also help to distinguish these diseases. With hyperplasia of the adrenal cortex, the following hormonal changes will be characteristic: an increase in the amount of 17-KS, DEA, androstenedione and etiocholanolan, pregnantriol and aldosterone with a decrease in urinary excretion of 11-OKS.

Various forms of AGS must be distinguished from tumors of the ovaries (androblastoma), adrenal glands (androsteroma), viril syndrome of hypothalamic origin and constitutional hirsutism.

Treatment of adrenogenital syndrome in various forms has much in common, depending on age and the nature of functional and anatomical disorders. In all forms, therapy should be started as early as possible before severe virilization, which helps to reduce androgen levels and normalize ovarian function and the entire neuroendocrine regulatory system. reproductive function. Glucocorticoid drugs are used.

Treatment of congenital AHS should begin at an early age before masculinization and bone growth arrest. The dose of glucocorticoid drugs depends on age: up to 2 years, cortisone is prescribed at 20 mg, prednisolone at 3 mg, dexamethasone at 0.5 mg per day; from 2 to 5 years - 30 mg, 5 mg and 1 mg, respectively; from 5 to 12 years - 50 mg, 10 and 2 mg, respectively, after 12-14 years at the adult dose: cortisone 50-100 mg, prednisolone 10-15 mg and dexamethasone 2-4 mg. Doses of drugs may increase or decrease depending on the effectiveness of the therapy, which is determined by clinical data and the level of hormones (17-KS, DEA, testosterone, etc.) in the blood.

Thus, a decrease in 17-CS up to 2-5 years of age is noted to 2-5 mg / day, at 6-12 years old - up to 4-6 mg and over 12 years old - up to 7-8 mg / day, as in adults . Clinically, under the influence of glucocorticoids in early childhood, there is normal development girls, then premature ossification of the epiphyseal bones is prevented (at 8-9 years old) and further growth in length continues, the degree of virilization decreases. Subsequently, the growth of the mammary glands and uterus is noted, the function of the ovaries is normalized and menstruation appears. Late initiation of treatment leads to the normalization of the genital organs, but their growth does not increase. Feminization occurs due to the normalization of the pituitary gland and the hormonal function of the ovaries. It is believed that under the influence of glucocorticoid hormones, the reverse development of the hypothalamus occurs along male type switching to female. Treatment with hormones large doses ah should be carried out within 1-2 years before the appearance pronounced effect, then in maintenance doses (prednisolone 2.5-5-10 mg) often throughout life. Stopping treatment leads to a relapse of the disease.

Surgical treatment for the correction of abnormal external genitalia is aimed at resection or extirpation of the clitoris (up to 5 years), dissection of the urogenital sinus and formation of the entrance to the vagina (up to 10 years of age).

Treatment of the salt-losing form of AGS is supplemented by the use of sodium chloride (5-7 g) in food, and sometimes the use of DOC (1-3 mg / day).

Due to the decrease in resistance and immune reactivity in the treatment of glucocorticoids in cases of infection or before surgery, the dose of drugs is increased.

In the treatment of patients with mild and moderate forms of AGS in the post-pubertal period with the development of hirsutism, amenorrhea and infertility, glucocorticoid therapy is carried out for 3-5 months (prednisolone 10-15 mg per day), and then continues in a maintenance regimen (prednisolone 2, 5-5 mg). Intermittent administration of drugs is possible: glucocorticoids for the first 10-15 days of the cycle, then progesterone 5-10 mg 6-8 days for 3-5 months and then maintenance therapy. According to the indications against the background of glucocorticoids, a cyclic hormone therapy steroid hormones (estrogens - gestagens), as well as the use of clomiphene and parlodel.

The prognosis with proper treatment of AGS is favorable for the restoration of sexual development, menstrual and generative function. special treatment constitutional hirsutism does not require.

Congenital dysfunction of the adrenal cortex (synonym: adrenogenital syndrome in children) includes a group of hereditary fermentopathies. At the heart of each of the fermentopathies is a genetically determined defect in the enzyme involved in steroidogenesis.

Defects in five enzymes involved in the synthesis of glucocorticoids and mineralocorticoids are described, which results in the formation of one or another variant of adrenogenital syndrome in children. All forms of congenital adrenal dysfunction are inherited in an autosomal recessive manner.

ICD-10 code

• E25 Adrenogenital disorders.
• E25.0 Congenital adrenogenital disorders associated with enzyme deficiency.
• E25.8 Other adrenogenital disorders.
• E25.9 Adrenogenital disorder, unspecified.

What causes adrenogenital syndrome in children?

In 90% of cases, a defect in 21-hydroxylase is observed, which may be due to various mutations in the CYP21 gene encoding this enzyme. Dozens of CYP21 mutations leading to the P450c21 defect have been described. There is also a point mutation with partial activity of 21-hydroxylase. With a partial deficiency of this enzyme, a simple (virile) form of the disease develops. 21-hydroxylase is involved in the synthesis of cortisol and aldosterone and is not involved in the synthesis of sex steroids. Violation of the synthesis of cortisol stimulates the production of ACTH, which leads to hyperplasia of the adrenal cortex. At the same time, 17-OH-progesterone, a precursor of cortisol, accumulates. Excess 17-OH-progesterone is converted into androgens. Adrenal androgens lead to virilization of the external genital organs in the female fetus - a girl is born with false female hermaphroditism. In boys, hyperandrogenemia determines the premature appearance of secondary sexual characteristics (precocious puberty syndrome).

With a significant deficiency of 21-hydroxylase, the hyperplastic adrenal cortex does not synthesize cortisol and aldosterone in the required quantities. at the same time, against the background of hyperandrogenemia, a syndrome of salt loss or adrenal insufficiency develops - a salt-losing form of the disease.

The non-classical form of 21-hydroxylase deficiency manifests itself in pre- and pubertal age in the form of adrenarche, moderate hirsutism, and menstrual irregularities in girls. Moderate or mild virilization in this case is the result of a point mutation of V281L and P30L.

Symptoms of adrenogenital syndrome in children

In the classical viril form of adrenogenital syndrome in children, the external genital organs of the girl are formed according to the heterosexual type - the clitoris is hypertrophied, the labia majora resemble the scrotum, the vagina and urethra are represented by the urogenital sinus. In newborn boys, no obvious abnormalities can be identified. From the age of 2-4, children of both sexes have other symptoms of adrenogenital syndrome in children, that is, androgenization: axillary and pubic hair is formed, skeletal muscles develop, the voice coarsens, the figure becomes masculinized, juvenile acne appears on the face and torso. In girls, the mammary glands do not grow, menstruation does not appear. At the same time, the differentiation of the skeleton is accelerated, and the growth zones close prematurely, which leads to short stature.

In the salt-wasting form of 21-hydroxylase deficiency, in addition to the symptoms described above, children from the first days of life have signs of adrenal insufficiency. Regurgitation appears first, then vomiting, loose stools are possible. The child quickly loses body weight, symptoms of dehydration, microcirculation disorders develop, blood pressure decreases, tachycardia begins, cardiac arrest due to hyperkalemia is possible.

The non-classical form of adrenogenital syndrome in children is characterized by early appearance secondary hair growth, acceleration of growth and differentiation of the skeleton. Girls puberty possible moderate signs hirsutism, menstrual disorders, the formation of secondary polycystic ovaries.

Insufficiency of 11-hydroxylase, in contrast to 21-hydroxylase deficiency, in addition to the symptoms of virilization and androgenization, is accompanied by an early and persistent increase in blood pressure. due to the accumulation in the blood of the precursor of aldosterone - deoxycorticosterone.

Diagnosis of adrenogenital syndrome in children

Laboratory diagnosis of adrenogenital syndrome in children

• All children with an abnormal structure of the external genital organs, including boys with bilateral abdominal cryptorchidism, are shown to determine the sex chromatin and study the karyotype.
• From the first days of life, an increased content of 17-OH-progesterone is found in the patient's blood serum. It is possible to conduct a screening test in newborns on the 2nd-5th day of life - 17-OH-progesterone is increased several times.
• Salt loss syndrome is characterized by hyperkalemia, hyponatremia, and hypochloremia.
• Urinary excretion of 17-ketosteroids (androgen metabolites) is increased.

Instrumental diagnosis of adrenogenital syndrome in children

• The bone age according to the radiograph of the wrist joints is ahead of the passport one.
• An ultrasound in girls reveals the uterus and ovaries.

Differential diagnosis of adrenogenital syndrome in children

In children of the first year of life, differential diagnosis of adrenogenital syndrome in children is carried out with various forms of false male hermaphroditism and true hermaphroditism. The reference point in the diagnosis is karyotyping (karyotype 46XX with a bisexual structure of the external genital organs) and the determination of 17-OH-progesterone in the blood serum. The salt-losing form of congenital adrenal dysfunction should be differentiated from pyloric stenosis, difficulties arise in the differential diagnosis of adrenogenital syndrome in children and pyloric stenosis in boys - in this case, hyperkalemia and high level 17-OH-progesterone in congenital dysfunction of the adrenal cortex.

In older children with symptoms of hyperandrogenemia, one should be aware of androgen-producing tumors of the adrenal glands or gonads.

Treatment of adrenogenital syndrome in children

Drug treatment of adrenogenital syndrome in children

The viril form of adrenogenital syndrome in children requires constant replacement therapy with prednisolone. The dose of the drug is selected individually depending on the age and degree of virilization and is divided into 2-3 doses. Its doses are distributed evenly throughout the day. Average daily dose prednisolone is 4-10 mg. This amount of the drug suppresses the excess production of androgens without causing side effects.

Treatment of the salt-wasting form of adrenogenital syndrome in children with a crisis of adrenal insufficiency is carried out in the same way as the treatment of acute adrenal insufficiency - by drip isotonic solution sodium chloride and glucose, as well as parenteral administration of hydrocortisone preparations (10-15 mg / kg per day). The daily amount of hydrocortisone is distributed evenly. The drug of choice is water-soluble hydrocortisone (Solucortef). When the condition stabilizes, hydrocortisone injections are gradually replaced with hydrocortisone tablets, if necessary, a mineralocorticoid - fludrocortisone (2.5-10.0 μg per day) is added.

Surgical treatment of adrenogenital syndrome in children

Girls at 4-6 years of age undergo surgical correction of the external genitalia.

Criteria for the effectiveness of the treatment of adrenogenital syndrome in children: normalization of the growth rate of the child, normal blood pressure, electrolytes in the blood serum. Optimal dose glucocorticosteroids is determined by the level of 17-OH-progesterone in the blood serum, mineralocorticoids - by the content of renin in the blood plasma.

Hereditary disease of the adrenal glands, in which steroidogenesis is impaired due to the functional failure of enzymes. It is manifested by virilization of the genitals, masculine-like physique, breast underdevelopment, hirsutism, acne, amenorrhea or oligomenorrhea, infertility. During the diagnosis, the levels of 17-hydroxyprogesterone, 17-ketosteroids, androstenedione, ACTH are determined, and ultrasound of the ovaries is performed. Patients are prescribed hormone replacement therapy with glucocorticoids and mineralocorticoids, estrogens in combination with androgens or new generation progestins. If necessary, plastic surgery of the genital organs is performed.

General information

Adrenogenital syndrome, or congenital dysfunction (hyperplasia) of the adrenal cortex, is the most common inherited disease. The prevalence of pathology differs among representatives of different nationalities. Classic options AGS in Caucasians occurs with a frequency of 1:14,000 infants, while in the Eskimos of Alaska this figure is 1:282. The incidence is significantly higher among Jews. Thus, a non-classical form of adrenogenital disorder is detected in 19% of Jewish people of the Ashkenazi group. Pathology is transmitted in an autosomal recessive manner. The probability of having a child with this syndrome when both parents carry the pathological gene reaches 25%, in the marriage of the carrier and the patient - 75%. If one of the parents has complete DNA, the clinical manifestations of the syndrome in children do not develop. If the father and mother have ADS, the child will also be sick.

Causes of adrenogenital syndrome

Symptoms of adrenogenital syndrome

In antenatal forms of the disease (simple viril and salt-losing), the main clinical symptom is visible virilization of the genitals. Newborn girls show signs of female pseudohermaphroditism. The clitoris is large in size or has a penis-like shape, the vestibule of the vagina is deepened, the urogenital sinus is formed, the large and small labia are enlarged, the perineum is high. The internal genital organs are developed normally. In infant boys, the penis is enlarged and the scrotum is hyperpigmented. In addition, with salt-losing adrenogenital disorder, symptoms of adrenal insufficiency are expressed with severe, often incompatible with life, somatic disorders (diarrhea, vomiting, convulsions, dehydration, etc.), which manifest themselves from 2-3 weeks of age.

In girls with simple virilous AGS, as they grow older, the signs of virilization intensify, and a dysplastic physique is formed. Due to the acceleration of ossification processes, the patients are characterized by short stature, broad shoulders, narrow pelvis, short limbs. Tubular bones are massive. Puberty begins early (up to 7 years) and proceeds with the development of secondary male sexual characteristics. There is an increase in the clitoris, a decrease in the timbre of the voice, an increase in muscle strength, and the formation of the typical for men form of the cricoid cartilage of the thyroid gland. The breast does not grow, the menarche is absent.

Less specific are clinical symptoms in non-classical forms of the virilizing syndrome that occur during puberty and after stressful loads (miscarriage in early pregnancy, medical abortion, surgery, etc.). Typically, patients remember that they still have in the younger school age there was a slight hair growth in the armpits and on the pubis. Subsequently, signs of hirsutism developed with the growth of rod hair over upper lip, along the white line of the abdomen, in the sternum, in the nipple-areolar zone. Women with AGS complain of persistent acne, porosity, and increased oiliness of the skin.

Menarche comes late - by 15-16 years. The menstrual cycle is unstable, the intervals between menstruation reach 35-45 days or more. Bloody discharge during menses scanty. The mammary glands are small. The clitoris is somewhat enlarged. Such girls and women may have high growth, narrow pelvis, broad shoulders. According to the observations of specialists in the field of obstetrics and gynecology, the later adrenogenital disorders develop, the less noticeable external signs, characteristic of men, and the more often the leading symptom becomes a violation of the monthly cycle. With rarer genetic defects, patients may complain of increased blood pressure or, conversely, hypotension with low performance and frequent headaches, skin hyperpigmentation with minimal symptoms of virilization.

Complications

The main complication of adrenogenital syndrome, for which patients turn to obstetrician-gynecologists, is persistent infertility. The earlier the disease manifested itself, the less likely get pregnant. With significant enzyme deficiency and clinical manifestations of simple virilizing syndrome, pregnancy does not occur at all. In pregnant patients with pubertal and post-pubertal forms of the disease, spontaneous miscarriages occur at an early stage. In childbirth, functional isthmic-cervical insufficiency is possible. Such women are more prone to the emergence of psycho-emotional disorders - a tendency to depression, suicidal behavior, manifestations of aggression.

Diagnostics

Diagnosis in antenatal types of AGS with characteristic changes in the genital organs is not difficult and is carried out immediately after childbirth. AT doubtful cases use karyotyping to confirm the female karyotype (46XX). Greater value diagnostic search acquires with a late clinical debut or hidden current with minimal external manifestations virilization. In such situations, the following laboratory and instrumental methods are used to detect adrenogenital syndrome:

• 17-OH-progesterone level. High concentration 17-hydroxyprogesterone, which is a precursor to cortisol, is a key sign of 21-hydroxylase deficiency. Its content is increased by 3-9 times (from 15 nmol/l and above).
• Steroid Profile (17-CS). An increase in the level of 17-ketosteroids in the urine of women by 6-8 times indicates a high content of androgens produced by the adrenal cortex. When performing a prednisolone test, the concentration of 17-KS decreases by 50-75%.
• Serum androstenedione content. Increased performance of this highly specific method laboratory diagnostics confirm the increased secretion of precursors of male sex hormones.
• Blood ACTH level. The classical forms of the disease are characterized by compensatory hypersecretion of adrenocorticotropic hormone by the anterior pituitary gland. Therefore, in virilizing dysfunction syndrome, the indicator is increased.
• ovarian ultrasound. In the cortical substance, follicles are determined at different stages of maturation, not reaching preovulatory sizes. The ovaries may be slightly enlarged, but there is no proliferation of the stroma.
• Measurement of basal temperature. The temperature curve is typical for anovulatory cycle: the first phase is stretched, the second is shortened, due to insufficiency corpus luteum, which is not formed due to the lack of ovulation.

The salt-losing variant of AGS is also characterized by an increased concentration of renin in the blood plasma. Differential diagnosis of adrenogenital disorders that occurred during puberty and childbearing age is carried out with polycystic ovary syndrome, ovarian androblastomas, adrenal androsteromas, viril syndrome of hypothalamic origin and constitutional hirsutism. In difficult cases, endocrinologists, urologists, and geneticists are involved in the diagnosis.

Treatment of adrenogenital syndrome

The main way to correct virilous dysfunction of the adrenal glands is hormone replacement therapy, which compensates for the deficiency of glucocorticoids. If a woman with occult AGS has no reproductive plans, skin manifestations hyperandrogenism is insignificant and menstruation is rhythmic, hormones are not used. In other cases, the choice of treatment regimen depends on the form endocrine pathology, the leading symptomatology and the degree of its severity. Often, the appointment of glucocorticoid drugs is supplemented with other medical and surgical methods, selected in accordance with a specific therapeutic goal:

• Infertility treatment. If there are plans for childbearing, a woman under the control of blood androgens takes glucocorticoids until full recovery ovulatory cycle and pregnancy. In resistant cases, ovulation stimulants are additionally prescribed. To avoid miscarriage, hormone therapy is continued until the 13th week of gestational age. In the first trimester, estrogens are also recommended, in II-III - progesterone analogues that do not have an androgenic effect.
• Correction of irregular periods and virilization. If the patient does not plan pregnancy, but complains of menstrual disorders, hirsutism, acne, estrogenic and antiandrogenic drugs are preferable, oral contraceptives containing the latest generation of progestogens. Therapeutic effect achieved in 3-6 months, however, at the end of treatment in the absence of hormone replacement therapy, signs of hyperandrogenism are restored.
• Treatment of congenital forms of AGS. Girls with signs of false hermaphroditism are given adequate hormonal therapy and surgical correction of the shape of the genital organs - cliterotomy, intraitoplasty (opening the urogenital sinus). With salt-losing adrenogenital disorders, in addition to glucocorticoids under the control of renin activity, mineralocorticoids are prescribed with an increase in therapeutic doses with the occurrence of intercurrent diseases.

Certain difficulties in the management of the patient arise in cases where the disease is not diagnosed in an obstetric hospital, and a girl with severe genital virilization is registered and brought up as a boy. When deciding to restore female gender identity, surgical plastic surgery and hormone therapy are supplemented with psychotherapeutic support. The decision to preserve the civilian male and remove the uterus with appendages is made in exceptional cases at the insistence of the patients, but this approach is considered erroneous.

Forecast and prevention

The prognosis for timely detection of adrenogenital syndrome and adequately selected therapy is favorable. Even in patients with significant genital virilization after plastic surgery possible normal sex life and natural childbirth. Replacement Hormone Therapy in any form of AGS, it contributes to rapid feminization - the development of mammary glands, the appearance of menstruation, the normalization of the ovarian cycle, and the restoration of generative function. Prevention of the disease is carried out at the stage of pregnancy planning.

If there were cases in the family similar pathology, genetics consultation is indicated. Testing with ACTH for both spouses allows diagnosing heterozygous carriage or latent forms of adrenogenital disorder. During pregnancy, the syndrome can be detected by the results of a genetic analysis of chorionic villus cells or the contents of amniotic fluid obtained by amniocentesis. Neonatal screening, carried out on the 5th day after childbirth, is aimed at identifying an increased concentration of 17-hydroprogesterone for a quick choice of therapeutic tactics.

This pathological form is also known as congenital adrenal hyperplasia, or congenital adrenal dysfunction (as opposed to acquired adrenogenital syndrome, which is usually associated with the presence of a tumor of the adrenal cortex). In previous years, congenital adrenal hyperplasia was interpreted as pseudohermaphroditism (virile syndrome) in girls and macrogenitosomia praecox (false early puberty) in boys.

Etiology

Pathogenesis

A number of studies conducted in the same years made it possible to establish that various clinical variants of adrenogenital syndrome are determined by blocks of enzyme systems at certain stages of the synthesis of corticosteroids.

The first of the blocks in the way of the synthesis of corticosteroid hormones was identified at the stage of conversion of cholesterol to pregnenolone. Such a lesion is extremely rare. The formation of all types of hormones is disrupted, and as a result, total adrenocortical insufficiency occurs, incompatible with life. The baby dies either in the womb or immediately after birth. Due to the loss of the normal effect of androgens on the urogenital development of the fetus, the female-type Müllerian duct system remains undifferentiated even with the male genotype. Therefore, a child born with such an enzymatic disorder has a female-type external genitalia, but in reality is a male pseudohermaphrodite. A very characteristic feature of this variant of adrenogenital syndrome is lipoid hyperplasia of the adrenal cortex, ovaries or testicles.

The most common type of perinatal adrenogenital syndrome is a condition caused by an oxidative blockade. With a deficiency of the enzyme 21-hydroxydase, the normal formation of 11-deoxycortisol and cortisol from 17alpha-hydroxyprogesterone and 11-deoxycorticosterone from progesterone is disrupted (with a deficiency in the formation of aldosterone as well). In about 2/3 of cases, this block is partial, and then enough aldosterone is formed to minimize sodium loss, and cortisol formed in small amounts prevents serious symptoms of adrenal insufficiency. However, freely synthesized androgens, constantly stimulated by an excess of ACTH, cause masculinization. child's body with a significant increase in the penis in boys and the development of false hermaphroditism in girls.

Under the influence of hyperproduction of ACTH, progesterone derivatives are also intensively formed, of which the most characteristic is an increase in the content of pregnantriol, which is excreted into the urine per day in an amount of more than 2 mg (the highest limit of normal). In about 1/3 of patients with adrenogenital syndrome, the formation of cortisol and aldosterone is very low, and then a picture of a severe, salt-losing type of adrenogenital syndrome unfolds.

Finally, blocking the enzyme that provides 11-hydroxylation disrupts the synthesis of cortisol and aldosterone. But since 11-deoxycorticosterone (a precursor of aldosterone) is formed in excess, which itself has a pronounced mineralocorticoid activity, the electrolyte balance of the body is not disturbed and hypertension develops. Therefore, in this variant of congenital adrenal hyperplasia, masculinization phenomena are combined with hypertensive syndrome. It has been proven that in the hypertensive form of adrenogenital syndrome, the adrenal cortex also secretes a large number of compounds "S-Reichstein" or 11-deoxycortisol, which is excreted in the urine as the substance "tetrohydro-S". There is usually little pregnantriol in the urine.

Thus, with excessive production of androgenic hormones due to a violation of the biosynthesis of cortisol in the daily urine, the content of androgens, which are excreted as 17-ketosteroids, increases. The question of which androgenic compound or group of compounds with androgenic activity plays a role in congenital adrenal hyperplasia has not yet been finally clarified.

Congenital adrenogenital syndrome in an 11-month-old girl. a - appearance child, b - clitoral hypertrophy

Symptoms of congenital adrenogenital syndrome

The most common is the virilous form of the disease. Symptoms of the disease in girls usually appear already at birth, less often in the first years. postnatal period. In boys, penis growth and body hair develop in the 2nd or 3rd year of life, making it difficult early diagnosis diseases.

As mentioned above, in girls, a simple viril type of adrenogenital syndrome is expressed in a picture of false hermaphroditism. Already from birth, an enlarged clitoris is found, which, gradually increasing, begins to take the form of a male penis. The urinary opening opens, however, at the base of the penis-shaped clitoris. Could be urogenital sinus. Large shameful lips look like a split scrotum. Changes in the external labia are sometimes so pronounced that it is difficult to determine the sex of the child. If we add to this that a girl already at the age of 3-6 years has excessive hair growth on her pubis, legs, back, physical development accelerates, increases muscle strength and the male architectonics is strongly emphasized, it is not surprising that the child is often mistaken for a boy with bilateral cryptorchidism. Such a transformation of the female body into a male one can only be in the absence of proper treatment. As for the violation of the genital organs, according to the recommendations of Wilkins, three degrees of these changes should be distinguished: I degree - the disease developed in the second half of the prenatal period, there is only a hypertrophied clitoris, II degree - the end of the first half of pregnancy, in addition to the enlarged clitoris, there is a urogenital sinus , III degree - dysfunction of the adrenal glands occurred in the first months of intrauterine life of the fetus, the external genitalia are formed according to the male type. This means that the earlier hypersecretion of androgens occurs in the prenatal period, the more the genitals will be changed. Most often you have to deal with the III degree of changes in the external genital organs.

Naturally, in such girls, puberty does not occur in the future, mammary glands do not appear and menstruation is absent.

In boys, as noted, adrenogenital syndrome begins to manifest itself only from 2-3 years. Since that time, there has been an increased physical and false puberty of the child. Rapid growth, increased development of muscles, enlargement of the penis, excessive hair growth, the appearance of pubic hair make such a child look like an adult man. Early developed boys may have erections, sometimes there is a sexual feeling, but in the presence of a child's psyche. Naturally, in such children, the testicles are in an infantile state and do not develop further.

In both girls and boys, accelerated growth eventually stops due to the early closure of the epiphyseal growth zones. As a result, such children, despite the high growth rate in the first years of life, remain short in the future.

Somewhat less often, congenital adrenogenital syndrome can be combined with a significant electrolyte imbalance. Wilkins would classify this as salt-wasting adrenogenital syndrome.

Along with the symptom complex of virilism, indicating hyperproduction of corticosteroids with androgenic activity, these children have reduced glucocorticoid and mineralocorticoid functions of the adrenal cortex. The origin of electrolyte imbalance in adrenogenital syndrome is not fully understood. It is suggested that there is a deficiency (or absence) of the hormone that retains salt in the body - aldosterone. So, in 1959, Blizzard and Wilkins found that with a simple viril form of the disease, aldosterone secretion occurs normally; in the salt-losing form of adrenogenital syndrome, the level of aldosterone in the blood was lowered. At the same time, Prader and Velasco in 1956 noted the possibility of secretion by the adrenal cortex of hormones that increase the excretion of sodium from the body. These hormones appear to be distinct from aldosterone.

Macrogenitosomia in a 3-year-old boy with congenital adrenogenital syndrome.

Thus, the salt-losing type of adrenogenital syndrome is a typical example of congenital dysfunction of the adrenal cortex: on the one hand, increased release of androgens into the blood, on the other hand, a deficiency in the production of cortisol and mineralocorticoids.

Symptoms of salt wasting syndrome usually develop in children in the first weeks or in the first year of life. This form is more common in boys. The course of the disease is severe and is associated with increased excretion of sodium and chlorides from the body and simultaneous hyperkalemia. Patients develop repeated vomiting, exicosis occurs, and weight decreases. The child is irritable at first, but can quickly fall into a state of prostration: facial features are sharpened, the skin is grayish-dark, collapse occurs and, if vigorous treatment is not started, the patient dies. This condition sometimes develops acutely according to the type of Addisonian crisis. In addition, death may occur suddenly and without prior collapse. Apparently, in such cases, it is the result of hyperkalemia. Even receiving appropriate therapy (cortisone, salt), a child with a salt-losing form of adrenogenital syndrome is not guaranteed against acute development crisis. This is possible, for example, with the addition of an intercurrent infection. The introduction of cortisone in addition to the previously prescribed dose and saline quickly levels the patient's condition.

In such cases, pediatricians often suggest pyloric stenosis or acute toxic dyspepsia. Parenteral administration of a saline solution to these children temporarily improves the patient's condition, but without the systematic administration of cortisone, a relapse of the disease occurs again. Correct recognition of the nature of the disease is facilitated in cases where girls simultaneously have a picture of pseudohermaphroditism. In boys, the diagnosis is complicated by the fact that their virilization occurs later, and the somewhat hypertrophied penis in the newborn is not paid due attention.

The diagnosis is decided by an increased content of 17-ketosteroids in the urine for a given age. Helps in the diagnosis of high plasma levels of potassium and low sodium. The electrocardiogram often has a typical hyperkalemia appearance.

The third type of adrenogenital syndrome is quite rare - its hypertonic form. It is caused by a violation of 11-C-hydroxylation at the last stage of cortisol synthesis with excessive release of deoxycorticosterone into the blood, which can increase blood pressure. These patients, in addition to hypertension, have all the symptoms of the viril syndrome. Cortisone therapy contributes to lowering blood pressure in patients.

Thus, adrenogenital syndrome in children is a congenital dysfunction of the adrenal cortex. All forms are characterized by a deficiency in the formation of hydrocortisone (cortisol). In the salt-losing form, in addition, the synthesis of mineralocorticoids is impaired, and in the hypertonic type, the precursor of aldosterone, deoxycorticosterone, is intensively formed.

Despite the fact that cortisol synthesis is impaired in congenital dysfunction of the adrenal cortex, disorders carbohydrate metabolism are rare. However, hypoglycemia with repeated hypoglycemic crises (without electrolyte disturbances) is possible.

Partial hypocorticism can be expressed in skin pigmentation, which is often observed in such patients. In addition, in a number of children, even with a compensated form of adrenogenital syndrome, under the influence of stress, relative adrenal insufficiency can manifest itself in weakness, hypotension, and muscle pain. If patients have impaired electrolyte regulation even in a latent form, a typical salt-losing crisis occurs under the influence of stress.

It has already been pointed out that with congenital hyperplasia of the adrenal cortex, adrenogenital syndrome can be detected only in the postnatal or prepubertal period. This question has not yet been studied enough. In such cases, a differential diagnosis should always be made with acquired adrenogenital syndrome caused by an androgen-active tumor of the adrenal gland or ovary.

Diagnostics

From laboratory methods studies, the most widely used is the determination in the daily urine of the content of neutral 17-ketosteroids. With congenital hyperplasia and with tumors of the adrenal cortex, as a rule, their number is significantly increased, and in direct accordance with the degree of virilization. At 10-12 years old, daily urine can contain up to 30-80 mg of 17-ketosteroids, which significantly exceeds age norm(up to 10 mg per day).

As a rule, with adrenogenital syndrome, plasma adrenocorticotropic activity is significantly increased.

The level in the urine of total 17-hydroxycorticosteroids in congenital adrenogenital syndrome and in tumors of the adrenal cortex is different. With tumors, the indicators are often elevated (but not always), with congenital dysfunction of the adrenal cortex - normal or low.

Partial disruption of the synthesis of cortisol in adrenogenital syndrome leads to the excretion in the urine of its metabolic products - tetrahydro derivatives. However, more often there is a more severe violation of the synthesis of cortisol, which leads to the release of metabolites of intermediate products of the synthesis of cortisol - progesterone and 17-hydroxyproheterone. This occurs when 21-hydroxylation is disturbed, and therefore, in the diagnosis of congenital adrenogenital syndrome, it is important to determine the products of progesterone and 17-hydroxyprogesterone. These products are pregnandiol (progesterone metabolite) and pregnanetriol and pregnantriolon (17-hydroxyprogesterone metabolites).

All these metabolites appear in the urine in significant amounts already in the early stages of the disease, and their presence indicates blockade of 21-hydroxylation. It has been established that pregnandiol, pregnantriol and pregnantriolon can accumulate in the urine in case of virilizing adrenal adenomas, which should be taken into account in the differential diagnosis of the viril syndrome.

As can be seen from the above, it is sometimes difficult to carry out a differential. diagnosis between a tumor of the adrenal cortex and their hyperplasia. This is especially difficult with the late development of virilization. Very facilitates the task suprarenoregenography. But the tumor can occur very early and, in addition, it is sometimes so small that it is not detected on x-rays. At present, the cortisone test is of great importance. If a patient with adrenogenital syndrome is administered 50-100 mg of cortisone per day for 5 days (or in an appropriate dose of prednisone, prednisolone or dexamethasone), then the daily excretion of 17-ketosteroids in the urine will significantly and steadily decrease. In the presence of a virilizing tumor of the adrenal cortex, urinary excretion of 17-ketosteroids does not fall. This indicates that the production of androgens in the adrenal cortex does not depend on increased secretion of ACTH into the blood. Administration of cortisone to patients with congenital adrenogenital syndrome can also reduce urinary excretion of pregnantriol.

Congenital adrenogenital syndrome should be differentiated from all types of premature sexual development: cerebral-pituitary, ovarian or testicular origin. Precocious puberty of the constitutional type or dependent on the defeat of the interstitial-pituitary region will always be true, of the isosexual type. The increase in urinary 17-ketosteroids is moderate and never exceeds adolescent levels. In the urine, an increased content of gonadotropins is found. The testicles in boys increase to the size of adults, while in adrenogenital syndrome they are underdeveloped. In doubtful cases great importance has a testicular biopsy. With adrenogenital syndrome, immature tubules and the absence of Leydig cells are found, and with other types of early sexual development, a large number of Leydig cells and spermatogenesis are found. Precocious puberty in boys is rarely associated with the presence of an interstitial cell tumor of the testis. In these cases, there is a unilateral increase in the size of the testicle; on palpation, it is dense and bumpy; the second testicle may be hypoplastic. Biopsy followed by histology of testicular tissue decides the diagnosis.

In girls, premature sexual development extremely rarely can be caused by a granulosa cell tumor of the ovary. However, this tumor is estrogen-active and premature sexual development occurs according to the female type (with adrenogenital syndrome - according to the male). Arrenoblastoma - an ovarian tumor - practically does not occur in girls with androgenic activity.

Treatment of congenital adrenogenital syndrome

With a simple (virile) form of the syndrome, cortisone (prednisone or prednisolone) significantly reduces the urinary excretion of 17-ketosteroids and biologically active androgens. In this case, the process of suppression can be maintained indefinitely, for a long time, by relatively small doses of the drug, which do not have a negative effect on the metabolism.

Treatment begins with relatively large doses of cortisone or its derivatives (so-called shock therapy), which can suppress the androgenic function of the adrenal glands. The degree of suppression of adrenal function is determined by the daily excretion of 17-ketosteroids and pregnantriol. This method can reduce the level of excretion of 17-ketosteroids in young children to 1.1 mg per day, in older children - up to 3-4 mg per day. The duration of "shock doses" of corticosteroids is from 10 to 30 days. Preferably intramuscularly administer cortisone acetate 10-25 mg per day to infants, 25-50 mg to children 1-8 years old and 50-100 mg per day to adolescents.

You can prescribe cortisone (and its derivatives in appropriate doses) and inside.

After achieving a certain effect, they switch to long-term maintenance therapy, and the desired dosage of the corticosteroid is set according to the level of urinary excretion of 17-ketosteroids. Cortisone is also prescribed intramuscularly (for example, half the "shock dose" 2-3 times a week) or orally (fractionally equal doses in an amount approximately twice the daily amount of the drug administered intramuscularly). Prednisone or prednisolone has an advantage over cortisone, since they more actively inhibit the production of ACTH by the anterior pituitary gland and, in addition, retain little salt in the body. For maintenance therapy, a dose of these drugs of 10-20 mg per day inhibits the excretion of 17-ketosteroids in the urine for a long time.

With salt-wasting syndrome, which occurs more often in children with congenital adrenal hyperplasia under the age of 4-5 years, urgent administration of table salt, cortisone and deoxycorticosterone (DOC) is required, and doses are prescribed in accordance with the severity of the disease. In case of acute loss of salt (flowing like an Addisonian crisis), hydrocortisone is administered intravenously at the rate of 5 mg (kg) per day and 0.5-1 mg (kg) per day DOC- 1000 ml with the addition of 20% sodium chloride solution per 1 kg of body weight. The rate of administration is 100 ml of liquid per hour. With the gradual development of the syndrome, 5 mg of cortisone per 1 kg of body weight can be recommended. If necessary, add DOC 2 mg per day with gradual increase drug doses. A good effect is provided by subcutaneous injections of crystals (100-125 mg each) of DOC, which is very slowly absorbed into the blood and maintains the electrolyte balance of the body. In hypertensive forms of the disease, DOC and other hormones that increase sodium and water retention should not be given to the patient. A good effect is achieved from the use of cortisone or prednisolone. It should be stated that if patients become ill, or are subjected to surgical intervention, doses of hormones are recommended to be increased, which is especially important for salt-losing forms of adrenogenital syndrome.

Here are 2 cases of congenital dysfunction of the adrenal cortex: a 6-year-old girl with a picture of false hermaphroditism and a 5-year-old boy with macrogenitosomia praecos.

First case:

Valya P., 6 years old, congenital adrenogenital syndrome.
a - front view; b - side view; c - sharply hypertrophied penis-shaped clitoris

Valya P., aged 6, entered children's department Institute of Experimental Endocrinology and Chemistry of Hormones AMS 26/XII 1964. The child has an irregular structure of the genital organs, premature hair growth in the pubic area. The girl was born at home from the second normal pregnancy. At. birth weight is normal, the clitoris is slightly enlarged. The girl started walking at 18 months; from 3 years marked fast growth.

On admission, height 131 cm, weight 25 kg 700 g. On the skin there are aspae vulgaris. On the pubis - pronounced male-type hair growth. There are no changes in the structure of the skeleton. Heart - without features, pulse 92 beats per minute, good filling, clear heart sounds. Arterial pressure 110/65 mm. changes internal organs not detected. The clitoris is penis-shaped, 3 cm long, erect. The urethra opens into the urogenital sinus at the root of the clitoris. There are labioruni scrotulae, in the thickness of which the testicles are not defined. A lentil-sized uterus was palpated rectally. Tumors in the small pelvis is not defined.

Data x-ray examination: the shape and size of the Turkish saddle are not changed, bone age corresponds to 12 years.

After a test with cortisone administered intramuscularly for 7 days, the daily amount of 17-ketosteroids decreased to 5.5 mg, dehydroepiandrosterone - to 0.4 mg, 17-hydroxycorticosteroids - to 26.6 mg.

The patient was prescribed prednisolone but 5 mg 2 times a day and the hormonal profile was once again examined. The daily amount of 17-ketosteroils was 2.4 mg, 17-hydroxycorticosteroids - 3-2 mg, pregnandiol - 1.7 mg, pregnantriol - 2.2 mg, dehydroepiandrosterone - 0.7 mg.

The girl was discharged on February 15, 1965. It was prescribed to constantly take prednisolone 5 mg 2 times a day under the control of her general condition, weight, blood pressure, and the content of 17-ketosteroids in the urine.

Diagnosis: congenital dysfunction of the adrenal cortex (adrenogenital syndrome), simple viril form.

Second case:
Vova R., aged 5 and a half, was admitted on December 16, 1964 to the children's department of the Institute of Experimental Endocrinology and Chemistry of Hormones of the Academy of Medical Sciences with complaints of accelerated physical and sexual development. The boy was born large - weight 4550 g. Until the age of 4, the child developed normally, but was ahead of his peers in growth. At the age of 5, the mother noticed an increase in the genitals; shortly thereafter, pubic hair appeared, growth accelerated significantly. Over the past year has grown by 15 cm.

Upon admission, the height is 129.5 cm, which corresponds to the height of a 9-year-old boy, weight 26 kg 850 g. Correct physique. Arterial pressure 105/55 mm. The penis is large, there is a blurred pubic hair. Sex glands in the scrotum. The left testicle is the size of a walnut, the right testicle is the size of a cherry. Differentiation of the bones of the hand corresponds to 12 years.

Excretion with urine per day reached 26.1 mg of 17-ketosteroids, 2.4 mg of 17-hydroxycorticosteroids, and 1 mg of dehydroepiandrosterone.

The boy underwent a cortisone test, which showed a decrease in the content of 17-ketosteroids in the urine to 9.2 mg per day.

Based on the investigations, a diagnosis of congenital adrenal dysfunction was made and treatment with prednisolone was prescribed. During treatment with prednisolone, the release of 17-ketosteroids decreased to 7 mg per day. The boy was discharged with a recommendation to take prednisolone 5 mg once a day under the control of weight, height, blood pressure and hormonal profile. Follow-up consultation after 4 months.

Attention parents! A forum about adrenogenital syndrome is open on our website.