Adrenogenital syndrome in girls. Adrenogenital syndrome - all features of the pathology

Adrenogenital syndrome(AGS) is a hereditary fermentopathy with congenital hyperplasia of the adrenal cortex. The pathology is based on a genetically determined disruption of the steroidogenesis process. AGS is characterized by hypersecretion of androgens by the adrenal glands, suppression of the production of gonadotropic hormones and glucocorticoids, and impaired folliculogenesis.

IN official medicine AGS is called Apère-Gamay syndrome. He's different hormonal imbalance in organism: excessive content androgens in the blood And insufficient amounts of cortisol and aldosterone. The consequences of the disease are most dangerous for newborns. Their body becomes full of androgens and low in estrogen - male and female sex hormones.

First Clinical signs diseases appear in children immediately after birth. In some, extremely in rare cases, AGS is detected in individuals aged 20-30 years. The prevalence of the syndrome varies significantly in ethnic groups: it is maximum among Jews, Eskimos and representatives of the European race.

A little anatomy

Adrenal glands - paired endocrine glands, located above top part human kidney. This body provides coordinated work all body systems and regulates metabolism. The adrenal glands, together with the hypothalamic-pituitary system, provide hormonal regulation of the vital functions of the body.

The adrenal glands are located in the retroperitoneum and consist of an outer cortex and an inner medulla. Cells of the cortex secrete glucocorticosteroid and sex hormones. Corticosteroid hormones regulate metabolism and energy, provide immune protection body, tone the vascular wall, help adapt to stress. IN medulla Catecholamines, biologically active substances, are produced.

Cortisol is a hormone from the group of glucocorticosteroids secreted by the outer layer of the adrenal glands. Cortisol regulates carbohydrate metabolism and blood pressure, protects the body from the influence of stressful situations, has a slight anti-inflammatory effect and increases the level of immune defense.

Aldosterone is the main mineralocorticoid produced by the glandular cells of the adrenal cortex and regulates water-salt metabolism in the body. It removes excess water and sodium from tissues into the intracellular space, preventing the formation of edema. By acting on kidney cells, aldosterone can increase circulating blood volume and increase blood pressure.

Classification

There are 3 clinical forms of AGS, which are based on varying degrees 21-hydroxylase deficiency:

21-hydroxylase

• Complete absence of 21-hydroxylase in the blood leads to the development of a salt-losing form. It is quite common and life-threatening. In the newborn's body, the water-salt balance and reabsorption in the renal tubules are disturbed, and excessive urination occurs. Due to the accumulation of salts in the kidneys, the functioning of the heart is disrupted, and jumps in blood pressure occur. Already on the second day of life, the child becomes lethargic, drowsy, and adynamic. Patients often urinate, regurgitate, vomit, and practically do not eat. Infants die from dehydration and metabolic disorders. In girls, phenomena of pseudohermaphroditism are observed.
• Partial 21-hydroxylase deficiency caused by the typical virile form of the syndrome. At the same time, against the background of normal levels of aldosterone and cortisol in the blood, the level of androgens increases. This pathology is not accompanied by symptoms of adrenal insufficiency, but is manifested only by sexual dysfunction. In girls, the clinical picture of the disease is much brighter than in boys. The first symptoms appear immediately after childbirth. The enlargement of the clitoris ranges from its slight hypertrophy to the full formation of the male penis. At the same time, the ovaries, uterus and the fallopian tubes develop normally. Late detection of pathology and lack of treatment leads to progression of the disease. In boys with AGS, the clinical picture is less pronounced. Their genitals are formed correctly at birth. Precocious puberty syndrome manifests itself clinically at 3-4 years of age. As the boy grows up, reproductive dysfunction progresses: oligo- or azoospermia develops.
• Atypical late or postpubertal form is acquired. It develops only in women who are sexually active and has a poor clinical picture, up to the complete absence of symptoms. The cause of the pathology is usually an adrenal tumor. Patients experience accelerated growth, an enlarged clitoris, acne, hirsutism, dysmenorrhea, polycystic ovary syndrome, and infertility. With this form of the syndrome there is a high risk of miscarriage and early death. Atypical form difficult to diagnose due to unclear symptoms and lack of severe dysfunction adrenal glands

Etiopathogenesis

AGS occurs in individuals with congenital deficiency of the enzyme C21-hydroxylase. In order for its quantity in the body to be maintained at an optimal level, a full-fledged gene is required, localized in the autosomes of the 6th chromosome. A mutation of this gene leads to the development of pathology - an increase in size and deterioration in the functioning of the adrenal cortex.

The syndrome is inherited in an autosomal recessive manner - from both parents at once. In a carrier of one mutant gene, the syndrome does not manifest itself clinically. Manifestation of the disease is possible only in the presence of defective genes in both autosomes of the 6th pair.

Patterns of hereditary transmission of adrenogenital syndrome:

1. Children born to healthy parents who are carriers of the mutant gene may inherit adrenal hyperplasia.
2. Children born to a healthy mother from a sick father are healthy carriers diseases.
3. Children born to a healthy mother from a father who is a carrier of the mutation will suffer from AGS in 50% of cases, and in 50% will remain healthy carriers of the affected gene.
4. Children born from sick parents will inherit this disease in 100% of cases.

In extremely rare cases, adrenogenital syndrome is inherited sporadically. The sudden onset of pathology is due to negative impact on the process of formation of female or male germ cells. In extremely rare cases, sick children are born to completely healthy parents. The cause of such anomalies can be tumors of the adrenal glands and hyperplastic processes in the glands.

Pathogenetic links of AGS:

• defect of the gene encoding the enzyme 21-hydroxylase,
• lack of this enzyme in the blood,
• disruption of the biosynthesis of cortisol and aldosterone,
• activation of the hypothalamic-pituitary-adrenal system,
• hyperproduction of ACTH,
• active stimulation of the adrenal cortex,
• increase in the cortical layer due to the proliferation of cellular elements,
• accumulation of cortisol precursor in the blood,
• hypersecretion of adrenal androgens,
• female pseudohermaphroditism,
• precocious puberty syndrome in boys.

Risk factors that activate the pathology mechanism:

1. taking strong drugs,
2. increased level of ionizing radiation,
3. long-term use of hormonal contraceptives,
4. injuries,
5. intercurrent diseases,
6. stress,
7. surgical interventions.

The causes of AGS are exclusively hereditary in nature, despite the influence of provoking factors.

Symptoms

Main symptoms of AGS:

• Sick children at an early age are tall and have a large body weight. As a child's body develops, their appearance changes. By the age of 12, growth stops and body weight returns to normal. Adults are short and thin in build.
• Signs of hyperandrogenism: a large penis and small testicles in boys, a penis-shaped clitoris and male-pattern hair in girls, the presence of others in girls male characteristics, hypersexuality, rough voice.
• Rapid growth with deformation of bone tissue.
• Unstable mental state.
• Persistent arterial hypertension in children, dyspepsia is a nonspecific symptom present in many diseases.
• Hyperpigmentation of the child's skin.
• Periodic convulsions.

The salting form is different severe course and is rare. The disease manifests itself:

1. sluggish sucking
2. decrease in blood pressure,
3. diarrhea,
4. severe vomiting
5. convulsions,
6. tachycardia,
7. microcirculation disorders,
8. weight loss,
9. dehydration,
10. metabolic acidosis,
11. increasing adynamia,
12. dehydration,
13. cardiac arrest due to hyperkalemia.

The salt-wasting form is characterized by hyperkalemia, hyponatremia, and hypochloremia.

The simple form of AGS in boys aged 2 years is manifested:

1. penis enlargement,
2. hyperpigmentation of the scrotum,
3. darkening of the skin around the anus,
4. hypertrichosis,
5. the appearance of an erection,
6. in a low, rough voice,
7. the appearance of acne vulgaris,
8. masculinization,
9. accelerated bone formation,
10. short in stature.

The post-pubertal form manifests itself in teenage girls:

1. late menarche,
2. unstable menstrual cycle with irregular frequency and duration,
3. oligomenorrhea,
4. hair growth in atypical places,
5. oily skin on the face,
6. enlarged and enlarged pores,
7. masculine physique,
8. micromastia.

Abortions, miscarriages, and undeveloped pregnancies can provoke the development of this form of AGS.
In girls, the classic virile form of AGS is manifested by the intersex structure of the external genitalia: a large clitoris and extension of the urethral opening onto its head. The labia majora resemble the scrotum, in armpits and pubic hair begins to grow early, skeletal muscles are developing rapidly. Pronounced AGS does not always make it possible to determine the sex of the newborn. Sick girls look very similar to boys. Their mammary glands do not grow, menstruation is absent or becomes irregular.

Children with AGS are monitored by pediatric endocrinologists. Using modern therapeutic techniques, specialists provide medication and surgery syndrome, which allows the child’s body to develop correctly in the future.

AHS is not a deadly disease, although some of its symptoms depress patients psychologically, which often ends in depression or a nervous breakdown. Timely detection pathologies in newborns allows sick children to adapt to society over time. When a disease is detected in children school age the situation often gets out of control.

Diagnostic measures

Diagnosis of AGS is based on anamnestic and phenotypic data, as well as the results of hormonal studies. During general examination assess the patient's figure, height, condition of the genital organs, and degree of hair growth.

Laboratory diagnostics:

• Hemogram and blood biochemistry.
• Study of the chromosome set - karyotype.
• Studying hormonal status using enzyme immunoassay, which shows the content of corticosteroids and ACTH in the blood serum.
• Radioimmunoassay determines the quantitative content of cortisol in the blood and urine.
• In doubtful cases, put correct diagnosis allows molecular genetic analysis.

Instrumental diagnostics:

1. Radiography of the wrist joints allows us to establish that the bone age of patients is ahead of the passport age.
2. An ultrasound reveals the uterus and ovaries in girls. Ultrasound of the ovaries is important diagnostic value. Patients are found to have multifollicular ovaries.
3. Tomographic examination of the adrenal glands allows us to exclude tumor process and determine the existing pathology. With AGS, the paired gland is noticeably increased in size, while its shape is completely preserved.
4. Radionuclide scanning and angiography are auxiliary methods diagnostics
5. Aspiration puncture and histological examination of the punctate with the study of cellular composition are performed in especially severe and advanced cases.

Neonatal screening is carried out on the 4th day after the birth of the child. A drop of blood is taken from the newborn's heel and applied to a test strip. The further tactics of managing a sick child depend on the results obtained.

Treatment

AHS requires lifelong hormonal treatment. For adult women, replacement therapy is necessary for feminization, for men it is carried out to eliminate sterility, and for children in order to overcome psychological difficulties associated with early development secondary sexual characteristics.

Drug therapy for the disease consists of the use of the following hormonal drugs:

• To correct the hormonal function of the adrenal glands, patients are prescribed glucocorticoid drugs - Dexamethasone, Prednisolone, Hydrocortisone.
• In case of miscarriage, Duphaston is prescribed.
• Estrogen-androgen drugs are indicated for women who do not plan pregnancy in the future - Diana-35, Marvelon.
• To normalize ovarian function it is necessary to take oral contraceptives with progestins.
• From non-hormonal drugs reduces hirsutism "Veroshpiron".

Crises of adrenal insufficiency can be prevented by increasing the dose of corticosteroids by 3-5 times. Treatment is considered effective if women's menstrual cycle has normalized, ovulation has occurred, and pregnancy has occurred.

Surgical treatment of AHS is performed for girls aged 4-6 years. It consists of correction of the external genitalia - vaginal plastic surgery, clitoridectomy. Psychotherapy is indicated for those patients who are unable to independently adapt to society and do not perceive themselves as a full-fledged person.

Prevention

If there is a family history of adrenal hyperplasia, everyone married couples consultation with a geneticist is necessary. Prenatal diagnosis consists of dynamic monitoring of a pregnant woman at risk for 2-3 months.

Prevention of AGS includes:

1. regular examinations by an endocrinologist,
2. newborn screening,
3. careful planning of pregnancy,
4. examination of future parents for various infections,
5. eliminating the impact of threatening factors,
6. visit to a geneticist.

Forecast

Timely diagnosis and high-quality replacement therapy make the prognosis of the disease relatively favorable. Early hormonal treatment stimulates proper development genital organs and allows you to preserve reproductive function in women and men.

If hyperandrogenism persists or cannot be corrected with corticosteroid drugs, patients remain short in stature and have characteristic cosmetic defects. This disrupts psychosocial adaptation and can lead to nervous breakdown. Adequate treatment allows women with classic AGS forms get pregnant, carry and give birth healthy child.

Video: presentation on adrenogenital syndrome

Video: adrenogenital syndrome, “Live Healthy” program

Divided into a congenital form, which is considered classical , and non-classical light forms, which include postpubertal And puberty . They are classified depending on hyperandrogenism and the level of C21-hydroxylase deficiency. With this disease, the adrenal glands produce an excessive amount of androgens, while the hormone gonadotropin is released in insufficient quantities. As a result, a significant disruption of the subsequent growth of follicles, as well as their maturation, occurs in the ovaries.

The main cause of adrenogenital syndrome is considered to be a congenital deficiency of an element such as C21-hydroxylase, a special enzyme involved in the synthesis of androgens produced in the adrenal cortex. This enzyme is formed in sufficient quantities under the influence of a gene that is located in the short arm of the autosome - pairs of chromosome 6 . Typically, inheritance of this disease is characterized by an autosomal recessive nature. If there is only one pathologically altered gene in the body, the disease may not develop, and only when the pathological genes are in different pairs of chromosomes can adrenogenital syndrome develop.

Symptoms of adrenogenital syndrome

At congenital form adrenogenital syndrome even during the period intrauterine development When the hormonal function of the adrenal glands is formed, an excessive amount of androgens is produced. Excess androgens lead to sexual differentiation, relating to a female fetus. By 9-11 weeks of intrauterine development, the fetus already has sexual structure and organs characteristic of the female body, although the external genitalia at this stage are just beginning to form. Wherein female phenotype formed from the initial type.

The female fetus and its external genitalia are affected by excessive production, resulting in a significant increase in the genital tubercle, which then takes the shape of a penis-shaped clitoris, the labiosacral folds merge and are shaped like a scrotum. The urogenital sinus opens under the deformed clitoris, not initially distributed to the vagina and urethra. Therefore, when a child is born, it is often incorrectly identified. gender. Since the gonads and ovaries acquire a female shape, congenital adrenogenital syndrome is often called false female hermaphroditism, during fetal development, hyperproduction of androgens leads to adrenal hyperplasia.

Children suffering from this disease require constant monitoring by pediatric endocrinologists. Modern medical techniques provide for timely surgical treatment of adrenogenital syndrome in order to surgically perform gender correction and further child developed according to female type. Nowadays, patients with adrenogenital syndrome characterized by a late form often turn to gynecologist-endocrinologists.

In the pubertal congenital form, C21-hydroxylase deficiency manifests itself during intrauterine development even during the pubertal period, when the hormonal function of the adrenal cortex only manifests itself. However, the disturbances are especially noticeable immediately before the girl’s first menstruation. And if usually in the population the first menstruation occurs at 12-13 years, then in girls with congenital adrenogenital syndrome, characterized by a pubertal form, the first menstruation occurs much later, only at 15-16 years.

The menstrual cycle with this disease is quite unstable, menstruation occurs irregularly, girls tend to oligomenorrhea. The interval between menstruation is significant, as a rule, it is 30-45 days.

Quite pronounced, quite often it manifests itself in the growth of shaft hair located along the white line of the abdomen, in the growth of hair above the upper lip according to the male principle, on the thighs and around the nipples. A large amount appears on the body sebaceous glands, suppuration of the hair follicles is often observed, the skin on the face becomes oily, the pores become enlarged and dilated. Girls suffering from the pubertal form of adrenogenital syndrome are distinguished by their rather tall stature and masculine build, broad shoulders and narrow pelvis, hypoplasticity of the mammary glands is observed. As a rule, the main complaints of such patients when turning to doctors is the occurrence of acne or complaints of irregular menstrual cycles.

With this post-pubertal form of the disease, the symptoms of adrenogenital syndrome in girls are noticeable only after puberty. Quite often, symptoms become pronounced after, during non-developing or after spontaneous. Expressed in violation menstrual cycle, the intervals between menstruation increase significantly, menstrual flow become scarce, and delays often occur.

In this case, hyperandrogenism is characterized by relatively mild signs of manifestation, hirsutism is almost not expressed and manifests itself only in slight hair growth on the white line on the abdomen, a little hair may be on the legs, near the nipples, or above the upper lip. The girl’s mammary glands develop in the same way as those of her peers, the physique is formed according to the female type, and metabolic disorders do not appear.

Diagnosis of adrenogenital syndrome

Adrenogenital syndrome can be identified using modern hormonal studies , and also when visual inspection. In this case, phenotypic and anamnestic data are taken into account, such as hair growth in places uncharacteristic for women, male physique, development of the mammary glands, condition and general form skin, enlarged pores and acne. Adrenogenital syndrome is characterized by a significant disruption of the synthesis of steroids on 17-OHP, therefore the presence of this disease is indicated by an increase in the level of hormones in the blood and the detection of two hormones - DHEA-S and DHEA, which are considered precursors of testosterone.

It is also necessary to determine the 17-KS indicator during diagnosis, detected by analyzing urine for the presence of androgen metabolites in it. During a blood test to diagnose adrenogenital syndrome, the level of the hormones DHEA-S and 17-OHP is determined. During a comprehensive examination, for a full diagnosis, it is necessary to consider the symptoms of hyperandrogenism and other work disorders endocrine system. In this case, the 17-CS indicator in the urine and the level of the hormones DHEA-S, T, 17-OHP, and DHEA must be detected twice - first before the test with other glucocorticoids, and then after its implementation. If the level of hormones during the analysis decreases to 70-75%, this indicates the production of androgens exclusively in the adrenal cortex.

Accurate diagnosis of adrenogenital syndrome includes Ultrasound of the ovaries, during which it is revealed anovulation , it can be determined if follicles are present various levels maturity, which do not exceed preovulatory sizes. As a rule, in such cases the ovaries are enlarged, but, unlike polycystic ovary syndrome, with adrenogenital syndrome there is neither an increase in the volume of the stroma nor the presence of small follicles directly under the ovarian capsule. In diagnosis, basal temperature measurement is often used, and the disease is indicated by the characteristic duration of the phases - the long first phase of the menstrual cycle and the short second phase.

During the treatment of adrenogenital syndrome, use glucocorticoid drugs, which can correct hormonal function in the adrenal glands. Quite often doctors use a drug such as dexamethasone , the daily dose of which should not exceed 0.5-0.25 mg. During treatment, regular monitoring of the level of androgens in the patient’s blood and metabolites in the urine is necessary. If after this the menstrual cycle returns to normal, the therapy can be considered successful and effective. After drug treatment there should appear ovulatory cycles, the presence of which can be detected by measuring basal temperature. If a change in the phases of the menstrual cycle and their normalization were detected, then in the middle of the menstrual cycle the woman may become pregnant.

But even during pregnancy it is necessary to continue therapeutic treatment glucocorticoids up to the 13th week to avoid spontaneous miscarriage. By this time, the placenta has already formed correctly, which will ensure the production sufficient quantity hormones necessary for correct formation fetus For patients suffering adrenogenital syndrome , careful monitoring by doctors is necessary at all stages of pregnancy, it is especially important full treatment in the first stages of fetal formation. Basal temperature must be measured daily until the 9th week of pregnancy, every two weeks is necessary ultrasound diagnostics to reveal myometrial tone and examine the condition of detachments of the ovum.

If the patient has previously had spontaneous miscarriages you need to take estrogen-containing drugs to significantly improve the blood supply to the embryo during intrauterine development. As preparation for pregnancy, women are prescribed the drug, the daily dose of which is 0.25-0.5 mg, or in an amount of 1-2 mg. The woman’s condition must be carefully monitored, especially attention should be paid to complaints of pain in the lower abdomen, as well as the presence of bloody discharge from the genitourinary tract.

Nowadays, with adrenogenital syndrome in the treatment of miscarriage, time I-II trimester use a drug that is an analogue natural. This drug is not characterized by an androgenic effect, which distinguishes it favorably from norsteroid drugs, the use of which can lead to masculinization of the fetus, especially females. This drug is also used to treat isthmic-cervical insufficiency , which is often a concomitant disease with adrenogenital syndrome.

If pregnancy, despite the therapy, does not occur, ovulation does not occur, and the duration of the phases of the menstrual cycle remains the same, in addition to glucocorticoid therapy, it is necessary to stimulate the onset of ovulation. For this purpose, it is used, prescribed in a dose of 50-100 mg at certain stages of the menstrual cycle. When a woman goes to the doctor only with complaints of excess male hair growth, irregular menstruation, or pustular rashes on the face and body, but is not interested in pregnancy, therapy is carried out with other drugs.

Typically, such products contain antiandrogens And , the most commonly used among them . If there is hirsutism in a single complex with it, it is prescribed cyproterone acetate , the dose of which is 25-50 mg per day. The course of treatment with this drug is designed for 12-14 days. Full drug treatment takes from three months to six months, only then the therapy becomes effective. But the cause of the pathology remains unresolved, so after stopping treatment, the symptoms of adrenogenital syndrome begin to appear again.

The use of glucocorticoids, which normalize ovarian function, does not lead to a significant reduction in hirsutism. To get rid of this problem, you need to take oral contraceptives with progestins, such as , , norgestimate . Among non-hormonal drugs, one can single out, which must be taken for six months, 100 mg daily, in this case, most patients experience a significant decrease hirsutism .

On postpubertal form of this disease for patients who do not want to become pregnant, hormonal drugs, as a rule, are not prescribed, especially if the delays are not long-term and the acne on the skin is very minor. If a woman needs to be prescribed hormonal contraceptives, preference should be given to drugs such as, gestodene , desogestrel , norgestimate , but taking such medications for more than a year in a row is not recommended.

Adrenogenital syndrome (AGS) – hereditary pathology, associated with insufficient production of enzymes by the adrenal cortex, accompanied by an excess of sex hormones and a lack of glucocorticoids. The average frequency of occurrence in the population is 1:5500.

Causes of the syndrome

Adrenal glands – paired organ the person who plays vital role in the normal functioning of hormonal systems and regulation of metabolism. The adrenal glands synthesize a number of vital hormones, the most famous of which are adrenaline and norepinephrine. The adrenal glands are closely connected with the hypothalamic-pituitary system, forming the common hypothalamic-pituitary-adrenal system hormonal regulation. A violation at any of these links inevitably leads to pathology at higher and lower levels.

Anatomically and functionally, the adrenal glands consist of a cortex and medulla (“substances”). The medulla produces the bulk of catecholamine hormones (adrenaline and norepinephrine). In the cortex, morpho-functionally divided into three parts (glomerular, zona fasciculata and reticularis), glucocorticoids, mineralcorticoids and sex hormones are actively produced. For the topic we are considering, two hormones are important. Cortisol is a glucocorticoid hormone produced by the zona fasciculata of the adrenal cortex, vital for metabolism (in particular, it regulates energy metabolism in the body by controlling glucose metabolism). Aldosterone is a human mineralcorticoid hormone produced by the zona glomerulosa of the adrenal cortex, which is the main mineralcorticoid hormone in the blood, controlling such important metabolic processes as regulation of blood pressure and control of circulating blood volume. It is with their deficiency that the pathology we are considering is associated.

The cause of adrenogenital syndrome is considered to be insufficient production of cortisol and aldosterone by the adrenal cortex, due to congenital deficiency of the enzymes: 21-hydroxylase, 11-hydroxylase, 18-hydroxylase, 77-hydroxylase, 20-22-desmolase. Insufficient production of the hormone activates work within the hypothalamic-pituitary-adrenal system, while ACTH hormone (the pituitary hormone that controls the production of cortisol by the adrenal cortex) begins to actively stimulate the cortex, trying to compensate for the deficiency of the hormone. Hyperplasia occurs (tissue enlargement due to the growth of cellular volume) of the adrenal cortex, which does not lead to an increase in the synthesis of cortisol and aldosterone, because there are not enough enzymes necessary for this. However, all enzymes are present for the synthesis of sex hormones, and excessive stimulation of the adrenal cortex also leads to stimulation of this synthesis. As a result, the level of cortisol and aldosterone was and remains low, while the level of sex hormones (androgens) increases sharply. This can be represented schematically like this:

Symptoms of adrenogenital syndrome:

Today, there are two main forms of adrenogenital syndrome:

1. Viril form is the most common form of adrenogenital syndrome. Associated with 21-hydroxylase deficiency. This form can be corrected if detected in a timely manner and on average accounts for 2/3 of all patients with this pathology.
2. Salt-wasting form - has a more severe course, is much less common, children without proper treatment die in the first months of life. The main symptoms include symptoms of dyspepsia, decreased blood pressure, etc. Because the symptoms are nonspecific, this form often remains undiagnosed.
3. Hypertensive form is a rather rare form that is not always classified as a separate group. In addition to persistent virilization, in this form persistent arterial hypertension begins to appear early, not controlled by taking “heart” medications, which, in the absence of proper treatment, can lead to renal failure and disorders of cerebral (cerebral) circulation.

Among the main symptoms are the following:

1. Retarded growth and body weight – patients in early childhood They are distinguished by relatively tall height and large body weight, but on average, by the age of 12 years of life, growth stops or slows down, and, as a result, in adulthood, patients are characterized by small stature. In addition, in early childhood, signs of early androgenization appear - in boys strong increase in the size of the penis with relatively small testicles, in girls - an increase in the size of the clitoris, female genital organs, early hair growth (hair growth with age acquires features similar to the male type), deepening of the voice, partial changes in mental behavior.
2. Persistent arterial hypertension - often manifests itself in early childhood, but the symptom itself cannot be considered pathognomonic. Only the combination of this clinical manifestation with symptoms of early androgenization and laboratory data can suggest adrenogenital syndrome.
3. Dyspeptic symptoms are a nonspecific symptom and may be present in many other pathologies.

Diagnostics:

1. Initial examination– attention is drawn to the obvious androgenization of the child, hair growth, deepening of the voice, and a pronounced increase in the size of the genital organs.
2. Clinical tests– discarding many other methods laboratory diagnostics we should mention such a popular method today as determining the level of 17-OPN (17-hydroxy-progesterone), 17-KS in urine (17-ketosteroids), high level ACTH, increased levels of DHEA (precursor of testosterone). Today the norm is considered to be:
0.6-0.8 ng/ml for 17-OPN
from 7.8 to 9.0 mg/day for 17-KS
from 7.2 - 63.3 pg/ml for ACTH
DEA 0.9-11.7 and µmol/l
Not all experts believe in specificity this method, however, it is still extremely often used for differential diagnosis.
3. Ultrasound – not the best informative method, you can assess the condition of the adrenal glands (extremely difficult with ultrasound).
4. X-ray – evaluate the points of ossification, their correspondence with age norm(as a rule, growth acceleration is observed).
5. It is necessary to carry out differential diagnosis with other pathologies: adrenal insufficiency of a different origin, variants of premature puberty, androgen-producing adrenal tumor.
6. MRI and CT – allows you to examine the area of ​​the adrenal glands, determine the existing pathology, and exclude a tumor process.

The influence of adrenogenital syndrome on pregnancy:

Pregnancy is quite possible, especially if timely diagnosis and timely initiation of treatment. Women with adrenogenital syndrome have certain problems with carrying a pregnancy (even late stages, up to placental abruption), however, with properly selected glucocorticoid therapy, bearing a healthy child is possible. Therapy cannot be interrupted during pregnancy. One of the main problems with adrenogenital syndrome remains androgenization of the fetus, because maternal androgens can freely pass through the uteroplacental barrier. As a result of this kind of exposure, girls may experience an enlargement of the clitoris; in more severe cases, sinus urogenitalis and female pseudohermaphroditism may develop. To avoid this, it is necessary to continue and adjust existing therapy under the supervision of an obstetrician-gynecologist-endocrinologist.

Treatment of adrenogenital syndrome:

1. Glucocorticoid drugs are most often used. Currently, dexamethasone is prescribed at a dose of 0.5-0.25 mg. per day under the control of blood androgens and their metabolites in the urine.
2. With the salt-wasting form, it is necessary to add mineralcorticoids to therapy.
3. Sometimes you have to resort to surgical methods of treatment - vaginal plastic surgery, clitoridectomy.

With timely treatment, the prognosis is usually favorable, however, unfortunately, cases of uncorrectable course options are not uncommon.

All treatment is only under the supervision of a highly qualified specialist!

Gynecologist-endocrinologist Kupatadze D.D.

• Which doctors should you contact if you have Adrenogenital syndrome?

What is Adrenogenital syndrome

Adrenogenital syndrome- a group of autosomal recessively inherited disorders of corticosteroid synthesis. More than 90% of all cases of adrenogenital syndrome are caused by 21-hydroxylase deficiency.

What causes Adrenogenital syndrome?

The 21-hydroxylase enzyme gene is located on the short arm of chromosome 6. There are two genes - the active CYP21-B gene, encoding 21-hydroxylase, and the inactive CYP21-A pseudogene. These genes are largely homologous. The presence of a homologous DNA sequence near the coding gene often leads to pairing disorders in meiosis and, as a consequence, to gene conversion (movement of an active gene fragment to a pseudogene), or to deletion of part of the sense gene. In both cases, the function of the active gene is impaired. On chromosome 6, next to the CYP21 genes, there are HLA genes, which are inherited codominantly, as a result of which all homozygous sibs will have an identical HLA haplotype

Pathogenesis (what happens?) during Adrenogenital syndrome

The pathogenetic essence of adrenogenital syndrome is the inhibition of the production of some corticosteroids while simultaneously increasing the production of others due to a deficiency of one or another enzyme that provides one of the stages of steroidogenesis. As a result of P450c21 deficiency, the process of transition of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone is disrupted.

Thus, depending on the severity of the enzyme deficiency, a deficiency of cortisol and aldosterone develops. Cortisol deficiency stimulates the production of ACTH, the effect of which on the adrenal cortex leads to its hyperplasia and stimulation of the synthesis of corticosteroids - steroidogenesis shifts towards the synthesis of excess androgens. Hyperandrogenism of adrenal origin develops. The clinical phenotype is determined by the degree of activity of the mutated CYP21-B gene. With its complete loss, a salt-wasting version of the syndrome develops, in which the synthesis of glucocorticoids and mineralocorticoids is disrupted. When moderate enzyme activity is maintained, mineralocorticoid deficiency does not develop due to the fact that physiological need in aldosterone is approximately 200 times lower than in cortisol. There are 3 variants of 21-hydroxylase deficiency:

• 21-hydroxylase deficiency with salt wasting syndrome;
• simple viril form (incomplete 21-hydroxylase deficiency);
• non-classical form (post-pubertal).

The prevalence of adrenogenital syndrome varies significantly among different nationalities. Among representatives of the European race, the prevalence of classical variants (salt waste and simple) of 21-hydroxylase deficiency is approximately 1 in 14,000 newborns. This figure is significantly higher among Jews (non-classical form of 21-hydroxylase deficiency - up to 19% of Ashkenazi Jews). Among Alaskan Eskimos, the prevalence of classic forms of 21-hydroxylase deficiency is 1 in 282 births.

Symptoms of Adrenogenital Syndrome

Salt-wasting form of 21-hydroxylase deficiency

1. Excess androgens beginning with early stages fetal development, in newborn girls causes the intersex structure of the external genitalia (female pseudohermaphroditism). The severity of the changes varies from simple hypertrophy of the clitoris to complete masculinization of the genitals: a penis-shaped clitoris with extension of the urethral opening onto its head. The structure of the internal genitalia in fetuses with the female genotype with adrenogenital syndrome is always normal. In boys, there is an increase in penis size and hyperpigmentation of the scrotum. If left untreated in the postnatal period, virilization progresses rapidly. The growth zones of bones quickly close, as a result of which adult patients, as a rule, have short stature. In girls, in the absence of treatment, primary amenorrhea is determined, associated with suppression of the pituitary-ovarian system by excess androgens.
2. Adrenal insufficiency(aldosterone and cortisol deficiency) is manifested by symptoms such as sluggish sucking, vomiting, dehydration, metabolic acidosis, and increasing adynamia. Electrolyte changes and dehydration characteristic of adrenal insufficiency develop. These symptoms in most cases manifest between the 2nd and 3rd weeks after the birth of the child. One of the manifestations of glucocorticoid deficiency is progressive hyperpigmentation.

Simple viril form of 21-hydroxylase deficiency develops as a result of moderate enzyme deficiency, while salt-wasting syndrome (adrenal insufficiency) does not develop. But a pronounced excess of androgens, starting from the prenatal period, causes the manifestations of virilization described above.

Non-classical (post-pubertal) form of 21-hydroxylase deficiency

Prenatal virilization of the external genitalia and signs of adrenal insufficiency are absent. Clinical picture varies significantly. Most often, this form of the syndrome is diagnosed in women reproductive age during a targeted examination for oligomenorrhea (50% of patients), infertility, hirsutism (82%), acne (25%). In some cases, any clinical manifestations and decreased fertility are virtually absent.

Diagnosis of Adrenogenital Syndrome

The main marker of 21-hydroxylase deficiency is high levels of the cortisol precursor 17-hydroxyprogesterone (17-OHPg). Normally it does not exceed 5 nmol/l. A 17-OHPg level greater than 15 nmol/L confirms 21-hydroxylase deficiency. In most patients with classic forms of adrenogenital syndrome, the level of 17-OHPg exceeds 45 nmol/l.

In addition, 21-hydroxylase deficiency is characterized by increased levels of dehydroepiandrosterone (DHEA-S) and androstenedione. The salt-wasting form typically exhibits an increase in plasma renin levels, reflecting aldosterone deficiency and dehydration. In classical forms, ACTH levels are also increased.

Treatment of Adrenogenital Syndrome

At classical forms children are prescribed tableted hydrocortisone in daily dose 15-20 mg/m2 body surface or prednisolone 5 mg/m2. The dose is divided into 2 doses: 1/3 dose in the morning, 2/3 dose at night for maximum suppression of ACTH production by the pituitary gland. For the salt-wasting form, it is additionally necessary to prescribe fludrocortisone (50-200 mcg/day). In case of severe concomitant diseases and surgical interventions the dose of glucocorticoids needs to be increased. If the diagnosis of the virile form of adrenogenital syndrome is made late, streets with a genetically female gender may need surgical interventions for plastic surgery of external genitalia. The postpubertal (non-classical) form of adrenogenital syndrome due to 21-hydroxylase deficiency requires therapy only in the presence of severe cosmetic problems (hirsutism, acne) or decreased fertility.

Forecast

In classical forms, it fully depends on the timeliness of diagnosis (prevents the development of pronounced structural disorders of the external genitalia in girls) and the quality of the replacement therapy, as well as the timeliness of plastic surgery on the external genitalia. Persistent hyperandrogenism or, conversely, an overdose of corticosteroids contributes to the fact that most patients remain short, which, along with possible cosmetic defects (masked figure in women), disrupts psychosocial adaptation. With adequate treatment, women with classic forms of adrenogenital syndrome (including salt-wasting syndrome) can achieve normal pregnancy.

The content of the article

Congenital virilizing adrenal hyperplasia is a genetically determined disease, the development of which is based on the inferiority of enzyme systems in the adrenal cortex, insufficient production of cortisol and increased production of 17-ketosteroids, which have androgenic properties. The disease occurs in people of both sexes.

Etiology of adrenogenital syndrome

Main etiological factor is a congenital deficiency of the adrenal enzyme systems.

Pathogenesis of adrenogenital syndrome

Back in prenatal period the fetus lacks the enzymes responsible for the production of cortisol in the adrenal glands. This leads to a deficiency of cortisol in the blood, which affects the weakening of its inhibitory effect on the production of corticotropin. The content of corticotropin in the blood increases, and therefore there is increased stimulation of the adrenal cortex with hyperplasia of the reticular zone and excessive production of androgens.
Androgens cause virilization of the child’s body: boys experience accelerated growth, premature puberty with enlargement of the penis and the appearance of sexual desire; in girls - underdevelopment of the mammary glands, vagina, uterus, deepening of the voice, etc. In cases of more significant deficiency of 21-hydroxylase, aldosterone production may decrease and salt-wasting syndrome may develop (increased excretion of sodium and chlorides in the urine, which leads to dehydration and arterial hypotension ).

Pathomorphology of adrenogenital syndrome

With adrenogenital syndrome, adrenal hyperplasia, hypotrophy or atrophy of the ovaries, uterus, testicles, etc. are detected.

Classification of adrenogenital syndrome

According to the time of development, prenatal (intrauterine) congenital virilizing hyperplasia of the adrenal cortex and postnatal forms are distinguished; By clinical course- viril, salt-wasting and hypertensive forms.

Clinic of adrenogenital syndrome

Manifestations of the disease are different and depend on the gender of the patient, time of onset and form of the disease.
The viril form is the most common. Its symptoms are due to the virilizing and anabolic effects of excess androgens. It manifests itself in girls from birth with signs of pseudohermaphroditism: hypertrophy of the clitoris, resembling a penis, underdevelopment of the labia minora, vagina and uterus, enlargement of the labia majora, urogenital sinus. Sometimes changes in the external genitalia are so pronounced that it is difficult to determine the sex of the child. At the age of 3 - 6 years, excess hair growth is observed on the pubis, back, physical development and muscle strength are increased. By appearance girls resemble boys. Further sexual development stops, the mammary glands are poorly developed, menstruation is scanty with an irregular cycle without ovulation or completely absent.
In boys, the virile form noticeably manifests itself from 2 to 3 years of age. They develop intensively physically, their penis enlarges, excessive hair growth appears, and erections may occur. The testicles are infantile, and in further development them stops.
Despite the fact that at first girls and boys grow rapidly, children remain short and stocky (early closure of the epiphyseal growth zones).
The salt-wasting form of the disease is less common; its manifestations can be found in newborns and children in the first year of life, more often in boys. Most characteristic symptoms: regurgitation, vomiting, rapid decline body weight, arterial hypotension, irritability. Due to a violation of water-electrolyte balance, there is a rapid loss of sodium (a consequence of reduced glycocorticoid and mineralocorticoid functions of the adrenal cortex), dehydration. Cyanosis, hyperkalemia, convulsions, and collapse often occur. A patient who does not receive treatment may die.
The hypertensive form of the disease is very rare. In addition to signs of virilism, it is characterized by persistent arterial hypertension with early changes in the vessels of the fundus and kidneys.
In front of everyone clinical forms diseases possible skin pigmentation Brown or the color of coffee with milk. In the blood - the content of corticotropin is increased, in the salt-wasting form - low level aldosterone, sodium, chlorides, high potassium, hypoglycemia occurs. Increased excretion of 17-K.C in urine is noted.

Diagnosis of adrenogenital syndrome

The diagnosis is established on the basis of characteristic clinical symptoms and data laboratory research. A diagnostic test with dexamethasone or prednisolone is also used. Genetic sex is determined by the results of a sex chromatin study.

Differential diagnosis of adrenogenital syndrome

Differential diagnosis is carried out with a tumor of the adrenal cortex (androsteroma), premature sexual development of hypothalamic-pituitary origin, tumors of the pineal gland, ovaries and testicles.

Prognosis of adrenogenital syndrome

The prognosis is favorable if the disease is diagnosed early and treatment is carried out systematically. Without timely replacement therapy, acute adrenal insufficiency may develop with sudden fatal.

Treatment of adrenogenital syndrome

The most rational use of corticosteroid drugs (cortisone and its derivatives), since the basis of the disease is a deficiency in the production of cortisol (hydrocortisone) and mineralocorticoids. Cortisone, prednisone, or prednisone markedly reduces the urinary excretion of 17-ketosgeroids and biologically active androgens. Treatment begins with large doses.
Preferably, intramuscular administration of cortisone acetate. Daily dose: 10 - 25 mg for children infancy; 25 - 50 mg for children 1 - 8 years old and 50 - 100 mg for adolescents. Cortisone and its derivatives can be prescribed orally in appropriate doses. The duration of treatment with large doses is either 10 to 30 days. With this treatment, it is possible to reduce the excretion of 17-ketosgeroids to 3.8 µmol/day in children early age and up to 10.4 - 13.9 µmol/day in older children. Subsequently, once the effect is achieved, treatment is continued with maintenance doses of corticosteroids, guided by the level of urinary excretion of 17-KS. Of the cortisone derivatives, prednisolone and prednisone are effective. Their advantage is a more active suppression of the secretion of corticosterone by the pituitary gland, they retain little sodium in the body, and are well tolerated by children. When prescribed in a daily dose of 10 - 20 mg, urinary excretion of 17-KS is suppressed for a long time.
In the salt-wasting form, urgent administration of sodium chloride, cortisone and deoxycorticosterone is indicated. Usually, 5 mg/kg/day of hydrocortisone, 0.5 - 1 mg/kg/day of DOXA, and 1000 ml of 5% glucose solution with the addition of 20% sodium chloride solution (no more than 4 - 8 g/day) are administered intravenously. With the gradual development of the syndrome, it is sufficient to administer 5 mg/kg with the addition of 3 - 5 g/day of sodium chloride; if necessary, add DOXA 2 mg/day with a gradual increase in the dose of the drug.
In hypertensive forms, the administration of DOX and other hormones is not required, since they retain sodium and water. In such cases, you can limit yourself to prescribing prednisolop.
Timely and systematic (before the end of puberty) treatment with glycocorticoids prevents premature sexual development and promotes normal development testicles, eliminates the development of adrenal insufficiency, normalizes blood pressure. This treatment is carried out under the control of height, body weight, blood pressure, bone age. Anomalies in the development of the genital organs in girls are eliminated by corrective operations no earlier than after a year of treatment with glycocorticoids.