Adrenogenital syndrome: causes, signs, diagnosis, treatment, prognosis. Adrenogenital syndrome: a disease in newborns

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

AT official medicine AGS is called Apert-Gamet syndrome. It is characterized by hormonal imbalance in the body: excess levels of androgens in the blood and insufficient amounts of cortisol and aldosterone. The consequences of the disease are the most dangerous for newborns. In their body, there are a lot of androgens and few estrogens - male and female sex hormones.

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

A bit of anatomy

The adrenal glands are paired endocrine glands located above top human kidneys. This organ ensures the coordinated work of all body systems and regulates metabolism. The adrenal glands, together with the hypothalamic-pituitary system, provide hormonal regulation vital important functions organism.

The adrenal glands are located in the retroperitoneal space and consist of an outer cortical and an inner medulla. Cortical cells secrete glucocorticosteroid and sex hormones. Corticosteroid hormones regulate metabolism and energy, provide immune defense body, tone up vascular wall help to cope with stress. In the medulla, catecholamines are produced - biologically active substances.

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 the tissues into the intracellular space, prevents the formation of edema. By acting on the cells of the kidneys, aldosterone is able to increase the volume of circulating blood 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 the salt-losing form. It is quite common and life-threatening. In the body of a newborn is disturbed water-salt balance and reabsorption in renal tubules, there is excess urination. Against the background of the accumulation of salts in the kidneys, the work of the heart is disrupted, jumps occur blood pressure. Already on the second day of life, the child becomes lethargic, drowsy, adynamic. Patients often urinate, spit up, vomit, practically do not eat. Babies die from dehydration and metabolic disorders. In girls, the phenomena of pseudohermaphroditism are observed.
• Partial deficiency of 21-hydroxylase due to the typical viril form of the syndrome. At the same time, against the background of the normal content of aldosterone and cortisol in the blood, the level of androgens rises. This pathology is not accompanied by the phenomena 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. 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. Untimely detection of pathology and lack of treatment leads to the progression of the disease. In boys with AGS, the clinical picture is less pronounced. Their genitals are formed correctly at birth. The syndrome of premature puberty manifests itself clinically at 3-4 years. As the boy grows older, reproductive dysfunction progresses: oligo- or azoospermia develops.
• Atypical late or postpubertal form is purchased. It develops only in women who are active sexual life and has little clinical picture up to total absence symptoms. The cause of the pathology is usually a tumor of the adrenal glands. In patients, growth is accelerated, the clitoris is enlarged, acne, hirsutism, dysmenorrhea, polycystic ovaries, and infertility appear. With this form of the syndrome, the risk of miscarriage and early death is high. Atypical form difficult to diagnose, due to the ambiguity of symptoms and the absence of severe adrenal dysfunction.

Etiopathogenesis

AGS occurs in individuals with congenital deficiency of the C21-hydroxylase enzyme. To maintain its amount in the body at optimal level, requires a complete gene localized in the autosomes of the 6th chromosome. Mutation of this gene leads to the development of pathology - an increase in the size and deterioration of the functioning of the adrenal cortex.

The transmission of the syndrome by inheritance is carried out in an autosomal recessive way - immediately from both parents. In a carrier of one mutant gene, the syndrome does not manifest itself clinically. The 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 carry the mutated gene may inherit adrenal hyperplasia.
2. Children born to a healthy mother from a sick father are healthy carriers of the disease.
3. Children born to a healthy mother from a father with a mutation will have AGS in 50% of cases, and in 50% they 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 a negative impact on the formation of female or male germ cells. In extremely rare cases, sick children are born to absolutely healthy parents. The cause of such anomalies can be neoplasms of the adrenal glands and hyperplastic processes in the glands.

Pathogenetic links of AGS:

• a defect in the gene encoding the enzyme 21-hydroxylase,
• lack of this enzyme in the blood,
• violation of the biosynthesis of cortisol and aldosterone,
• activation of the hypothalamus-pituitary-adrenal system,
• hyperproduction of ACTH,
• active stimulation of the adrenal cortex,
• increase in the cortical layer due to the growth of cellular elements,
• accumulation of a precursor of cortisol in the blood,
• hypersecretion of adrenal androgens,
• female pseudohermaphroditism,
• syndrome of premature puberty 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. injury,
5. intercurrent diseases,
6. stress,
7. surgical interventions.

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

Symptoms

The main symptoms of AGS:

• Sick children at an early age have high growth and large body weight. As the child's body their appearance changes. By the age of 12, growth stops, and body weight returns to normal. Adults are characterized by short stature and a thin physique.
• Signs of hyperandrogenism: a large penis and small testicles in boys, a penis-shaped clitoris and male-type hair in girls, the presence of others in girls male signs, hypersexuality, rough voice.
• Rapid growth with bone deformity.
• Unstable mental state.
• Persistent arterial hypertension in children and dyspepsia - non-specific signs present in many diseases.
• hyperpigmentation skin child.
• Periodic convulsions.

The salt-losing form is severe and rare. The disease manifests itself:

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

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

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

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. low, rough voice
7. the appearance of acne vulgaris,
8. masculinization
9. accelerated bone formation
10. low stature.

The post-pubertal form manifests itself in adolescent girls:

1. late menarche,
2. unstable menstrual cycle with a violation of the 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. micromast.

Abortions, miscarriages, non-developing pregnancy can provoke the development of this form of AGS.
In girls, the classic viril 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. Large labia resemble the scrotum, in the armpits and on the pubis, hair begins to grow early, skeletal muscles develop rapidly. Pronounced AGS does not always allow you to determine the sex of the newborn. Sick girls outwardly are very similar to boys. They do not grow mammary glands, menstruation is absent or becomes irregular.

Children with AGS are under dispensary registration with pediatric endocrinologists. With the help of modern therapeutic techniques, specialists conduct medical and surgery syndrome, which allows further development of the child's body.

AGS is not fatal dangerous disease, although some of its symptoms psychologically depress patients, which often ends in depression or nervous breakdown. Early detection pathology in newborns allows sick children to adapt to society over time. When a disease is detected in school-age children, 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 a general examination, the patient's figure, height, condition of the genital organs, and the degree of hair growth are assessed.

Laboratory diagnostics:

• Hemogram and biochemistry of blood.
• Study of the chromosome set - karyotype.
• The study of hormonal status with the help 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.
• AT doubtful cases to make the correct diagnosis allows molecular genetic analysis.

Instrumental diagnostics:

1. Radiography wrist joints allows you to establish that the bone age of patients is ahead of the passport.
2. On ultrasound, the uterus and ovaries are found in girls. Ultrasound of the ovaries is important diagnostic value. Patients have multifollicular ovaries.
3. Tomographic examination of the adrenal glands allows you to exclude the tumor process and determine the existing pathology. With AGS, the steam gland is markedly enlarged in size, while its shape is completely preserved.
4. Radionuclide scanning and angiography are auxiliary methods diagnostics.
5. aspiration puncture and histological examination punctate with the study of the 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 heel of the newborn and applied to the test strip. Depends on the result further tactics management of a sick child.

Treatment

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

Drug therapy of the disease consists in 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-androgenic 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 the menstrual cycle has normalized in women, ovulation has appeared, and pregnancy has occurred.

Surgical treatment of AGS is carried out for girls aged 4-6 years. It consists in the correction of the external genital organs - the plastic of the vagina, clitorectomy. Psychotherapy is indicated for those patients who are not able to independently adapt in society and do not perceive themselves as a full-fledged person.

Prevention

If there is a family history of adrenal hyperplasia, all couples should consult a geneticist. Prenatal diagnosis consists in dynamic monitoring of a pregnant woman at risk for 2-3 months.

Prevention of AGS includes:

1. regular check-ups with an endocrinologist,
2. newborn screening,
3. careful planning of pregnancy,
4. examination of future parents for various infections,
5. exclusion of the impact of threatening factors,
6. visiting 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 save reproductive function in women and men.

If hyperandrogenism persists or cannot be corrected with corticosteroids, patients remain small in stature and have characteristic cosmetic defects. This disrupts psychosocial adjustment and can lead to nervous breakdown. Adequate treatment enables women with classic forms of AGS to become pregnant, bear and give birth to a healthy child.

Video: presentation on adrenogenital syndrome

Video: adrenogenital syndrome, the program “Live healthy”

It is subdivided into a congenital form, which is considered classical , and non-classical light forms, which include postpubertal and puberty . They are classified according to hyperandrogenism and the level of C21-hydroxylase deficiency. In this disease, the adrenal glands produce an excessive amount of androgens, while the hormone gonadotropin is secreted in insufficient quantities. As a result, in the ovaries there is a significant violation of the subsequent growth of follicles, as well as their maturation.

The main cause of adrenogenital syndrome is considered to be a congenital deficiency of such an element 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 the 6th chromosome . Typically, inheritance this disease differs in autosomal recessive character. 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

With a congenital form of adrenogenital syndrome, an excessive amount of androgens is produced during the formation of the hormonal function of the adrenal glands during the period of intrauterine development. An excess of androgens leads to sexual differentiation pertaining to the female fetus. By 9-11 weeks of intrauterine development, the fetus already has sexual structure and organs characteristic of female body although the external genitalia this stage are just beginning to take shape. In this case, the female phenotype is formed from the initial type.

The female fetus and its external genital organs are affected by excessive production, as a result, there is a significant increase in the genital tubercle, which then takes the form of a penis-shaped clitoris, the labiosacral folds merge and resemble the scrotum in shape. The urogenital sinus opens under the deformed clitoris, without initially spreading to the vagina and urethra. Therefore, at the birth of a child, its gender is often incorrectly determined. Since the gonads, the ovaries acquire female form, congenital adrenogenital syndrome is often called false female hermaphroditism, during fetal development, hyperproduction of androgens leads to hyperplasia of the adrenal glands.

Children with this condition need constant control by pediatric endocrinologists. Modern medical techniques provide for the timely surgical treatment of adrenogenital syndrome in order to perform a sex correction by surgery and in the future the child develops according to female type. Now patients often turn to gynecologists-endocrinologists in whom adrenogenital syndrome is characterized by a late form.

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

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

Quite pronounced, quite often it manifests itself in the growth of rod hair located along the white line of the abdomen, in the growth of hair above the upper lip along male principle, on the thighs and around the nipples. appears on the body a large number of sebaceous glands, often there is suppuration hair follicles, the skin on the face becomes oily, the pores increase and expand. Girls suffering from the pubertal form of adrenogenital syndrome differ quite tall and a male physique, broad shoulders and a narrow pelvis, there is hypoplasticity of the mammary glands. As a rule, the main complaints of such patients when contacting doctors is the occurrence acne or complaints about an irregular menstrual cycle.

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

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

Diagnosis of adrenogenital syndrome

Adrenogenital syndrome can be detected using modern hormonal studies, as well as at visual inspection. This takes into account phenotypic and anamnestic data, such as hair growth in places uncharacteristic for women, masculine physique, development of the mammary glands, condition and general form skin, enlarged pores and the presence of acne. Adrenogenital syndrome is characterized by a significant violation of the synthesis of steroids for 17-ONP, therefore, the presence of this disease is evidenced by an increase in the level of hormones in the blood and the detection of two hormones - DEA-C and DEA, which are considered precursors of testosterone.

It is also necessary to determine the indicator of 17-KS during the diagnosis, which is 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 DEA-C and 17-OHP is determined. With a comprehensive examination for a complete diagnosis, it is necessary to consider the symptoms of hyperandrogenism and other disorders in the endocrine system. At the same time, the indicator of 17-KS in the urine and the level of the hormones DEA-C, T, 17-ONP, and DEA must be detected twice - first before the test with and other glucocorticoids, and then after its implementation. If the level of hormones in the analysis decreases to 70-75%, this indicates the production of androgens exclusively in the adrenal cortex.

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

During the treatment of adrenogenital syndrome, glucocorticoid drugs, which can correct hormonal function in the adrenal glands. Quite often, doctors use a drug such as dexamethasone , daily dose 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, ovulatory cycles should appear, the presence of which can be detected by measuring basal temperature. If at the same time a change in the phases of the menstrual cycle and their normalization was revealed, then in the middle of the menstrual cycle a 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 is already correctly formed, which will ensure the production enough hormones necessary for the proper development of the fetus. Patients suffering from adrenogenital syndrome , careful observation by doctors is necessary at all stages of pregnancy, it is especially important complete treatment during the early stages of fetal development. Basal temperature must be measured daily up to the 9th week of pregnancy, every two weeks ultrasound diagnostics to reveal myometrial tone and examine the condition of the detachments of the fetal egg.

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 fetal development. As a preparation for pregnancy, women are prescribed a 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 spotting from the urinary tract.

Now, with adrenogenital syndrome, in the treatment of miscarriage, even during the I-II trimester, a drug is used that is an analogue natural. This drug is not characterized by an androgenic effect, which distinguishes it favorably from the norsteroid series, the use of which can lead to masculinization of the fetus, especially the female. This drug is also used to treat isthmic-cervical insufficiency , which is often 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, 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 excessive male hair, irregular menstruation, or pustular rashes on her face and body, but is not interested in pregnancy, therapy is carried out with other drugs.

As a rule, such funds contain antiandrogens and , the most commonly used among them . In the presence of 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. Complete drug treatment takes from three months to six months, only then the therapy becomes effective. But the cause of the pathology remains unresolved, therefore, after the treatment is stopped, the symptoms of adrenogenital syndrome begin to reappear.

The use of glucocorticoids, which allow normalizing ovarian function, does not lead to a significant decrease 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 the post-pubertal form this disease to patients who do not want to become pregnant, hormonal preparations, as a rule, are not prescribed, especially if the delays are not long-term, and acne on the skin is very minor. If a woman needs to be given 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.

"Adrogenital Syndrome"

Executor:

Wedge. Resident

Agaparyan E. R.

Moscow 2001

In diseases of the adrenal glands, virilism is most often caused by excessive production of androgens of adrenal origin, which is observed mainly in congenital adrenal cortex dysfunction (CHD), known to doctors such as congenital adrenogenital syndrome (AGS), congenital adrenal hyperplasia, false female hermaphroditism, or premature puberty heterosexual girls.

Adrenogenital syndrome is a hereditary congenital disease caused by the inferiority of the enzyme systems involved in the synthesis of steroid hormones of the adrenal cortex and leading to a decrease in cortisol production to varying degrees. At the same time, according to the mechanism feedback, increases the secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland, causing bilateral hyperplasia of the adrenal cortex and activation of the synthesis of hormones, mainly androgens.

Excess production of androgens is the main pathogenetic mechanism for the development of virilization of the female body, the manifestations of which depend on the degree of androgen secretion and the time of onset of pathology.

The incidence of AGS varies from 1 in 5000-10000 births (7). The frequency of the disease in families is 20-25%. AGS is inherited in an autosomal recessive manner. There are no changes in the karyotype, the level of sex chromatin remains normal or slightly elevated. It is possible to identify heterozygotes among parents and relatives. At the same time, changes in the biosynthesis of corticosteroids in heterozygotes are the same as in patients with AHS, but are much less pronounced.

Depending on the defect in the enzyme systems, 6 variants of VDKN are distinguished. A simplified diagram of the synthesis of steroids in the adrenal glands involved in the synthesis of enzyme systems is shown in the figure.

1. With a defect in the enzyme 20, 22 - desmolase, the synthesis of steroid hormones from cholesterol into active steroids is disrupted (aldosterone, cortisol and androgens are not formed). This leads to salt loss syndrome, glucocorticoid deficiency. Patients die in early childhood.

2. Deficiency of 3-ol-dehydrogenase leads to impaired synthesis of cortisol and aldosterone on early stages their formation, as a result of which a pattern of salt loss develops. Due to the partial formation of dehydroepiandrosterone (DHEA), the virilization of the body in girls is weakly expressed.

3. Deficiency of 17-hydroxylase causes a violation of the synthesis of sex hormones (androgens and estrogens) and cortisol, which leads to sexual underdevelopment, arterial hypertension, hypokalemic alkalosis.

4. Deficiency of 11-hydroxylase in the patient's body leads to a significant excess of 11-deoxycorticosterone, which has pronounced mineralocorticoid properties. Urinary excretion of 11-deoxycortisol and ketopregnantriol sharply increases. In this variant of the disease, along with virilization, which is less pronounced than in other congenital forms of AGS, there is high blood pressure, sodium and chloride retention.

5. Lack of enzyme 18-oxidase can only lead to aldosterone deficiency. Clinically, this is manifested by a severe salt-wasting syndrome, leading to death in early childhood.

6. With a deficiency of 21-hydroxylase, the clinical manifestations of the disease are due to the degree of completeness of the block of enzyme systems.

Synthesis block 21 - hydroxylase can be complete and partial. With an absolute block, the life of the organism is impossible. A partial block of 21 - hydroxylation (the defect is localized at the stage of conversion of 17 - hydroxyprogesterone to 11 - deoxycortisone) causes hyperproduction of 17 - hydroxyprogesterone and its main metabolite - pregnantriol (the latter appears in the urine), as well as steroids with androgenic properties (in particular, physiological active metabolites testosterone). Clinically, this variant of impaired steroidogenesis manifests itself with signs of virilization and is interpreted as a “virile (or simple)” form of AGS without noticeable glucocorticoid or mineralocorticoid deficiency. This form of the disease is the most common and occurs in 90-95% of all cases of congenital AGS. Severe insufficiency 21 - hydroxylation is accompanied, along with a violation of the synthesis of cortisol, a decrease in the synthesis of aldosterone. A defect in the enzymatic system manifests itself at the stage of the conversion of progesterone to 11 - deoxycorticosterone. A salt-losing form of congenital AGS develops, characterized by virilization and impaired water-salt metabolism, up to complete dehydration of the body.

Thus, two forms of deficiency of 21 - hydroxylase are currently described: classical or congenital and mild, the latter in turn includes latent form and late-onset syndrome (AGS of puberty and AGS of adults). Depending on the clinical manifestation the congenital form of AGS is divided into salt-losing, hypertonic, virilous.

Salt-wasting form.

The salt-wasting form of VDKN, along with pseudohermaphroditism in girls, which is a consequence of impaired synthesis of glucocorticoids, is characterized by a change mineral metabolism according to the type of insufficiency of the adrenal cortex. Signs of adrenal insufficiency (actual salt loss syndrome) are manifested in the form of hyponatremia, hyperkalemia, dehydration, arterial hypotension and hypoglycemia. Clinically, from the first days of life, a child develops profuse vomiting, which is not always associated with food intake. At less severe course, salt loss syndrome is manifested by anxiety, poor appetite, stopping weight gain, regurgitation. Then vomiting occurs, diarrhea joins, rapid weight loss, signs of dehydration. Cyanosis appears around the mouth and eyes, dry skin, muscular hypotension replaced by convulsions. Without treatment, patients die from vascular collapse. In milder cases, in the first months of life, the child lags behind in growth and development, hyperpigmentation of the skin, characteristic of adrenal insufficiency, is found. With age, the same virile changes appear as in the "classic" virile form.

hypertensive form.

In the hypertensive form of VDNK, in addition to the usual virilization, a violation develops of cardio-vascular system caused by long-term arterial hypertension. Prolonged arterial hypertension leads to cardiac and renal decompensation, sometimes complicated by a stroke. The degree of hypertension depends on the severity of the defect in the biosynthesis of hormones of the adrenal cortex, determined by the amount of secreted 11 - deoxycorticosterone and 11 - deoxycortisol.

The last two forms of the disease appear in the first days postnatal period accompanied by life-threatening symptoms. Children do not adapt well to the external environment and die at an early age, therefore, as a rule, they do not get to endocrinologists.

Endocrinologists and gynecologists more often observe children with a simple virilizing form of AGS, characterized by signs of false female hermaphroditism. The severity of the viril syndrome depends on age-related manifestations of enzyme anomalies, the intensity and duration of hyperandrogenization.

A simple virilous (congenital) form of AGS.

The degree of virilization in the congenital form depends on the embryonic period in which it developed, and can be different - from hirsutism to vivid heterosexuality. If a genetic defect in the enzyme systems involved in the synthesis of cortisol manifests itself already at the stage of embryogenesis, then along with a deficiency of cortisol in the developing organism, hyperproduction of androgens, hypertrophy of the adrenal cortex, and anomalies in the development of the genital organs are observed.

Depending on the period of ontogenesis, in which the hormonal function of the adrenal glands is disturbed, the symptoms of virilization are different. The earlier the female fetus is exposed to the action of androgens, the more severe the malformations of the external genitalia. Violation of sexual differentiation is expressed in clitoral hypertrophy and pathological changes in the urogenital sinus, up to pseudohermaphroditism, since the uterus, tubes and ovaries in such girls are determined. The ovaries are functionally active formations, according to morphological structure approaching normally functioning ovaries. The enlarged clitoris resembles a penis with hyspospadias, large labia due to pigmentation and folding - the scrotum. The scrotolabial folds fuse and sometimes the vagina opens like the urethra into the urogenital sinus, and the sinus in turn opens at the base of the clitoris. In some cases, the vagina flows into the urethra. It is quite difficult to solve social questions about gender, psychological adaptation in society and the family in such cases.

After the birth of a girl, androgen hyperproduction does not stop. In case of untimely diagnosis of the disease and the absence of appropriate treatment, hair growth of the pubis and armpits begins by the age of 3-4, hair appears on the face by the age of 8-10, and hirsutism develops by the age of 12-14. The mammary glands do not develop, primary amenorrhea is observed. The anabolic effect of androgens is manifested rapid growth and muscle development. Bone age ahead of the passport - usually at the age of 10 years, the epiphyseal fissures close, due to the cessation of the growth of long tubular bones, moderately pronounced dysplasia is noted - relatively short arms and legs, long torso. Muscle tissue develops well, which further emphasizes the athletic physique, children look like “little Hercules”. Adult patients are usually short (150-155 cm), physically well developed, have viril body features (narrow pelvis, broad shoulders).

The content of the article

Congenital virilizing hyperplasia of the adrenal cortex 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 - 17-ketosteroids with androgenic properties. The disease occurs in both sexes.

Etiology of adrenogenital syndrome

The pathogenesis of adrenogenital syndrome

Pathomorphology of adrenogenital syndrome

Classification of adrenogenital syndrome

Clinic of adrenogenital syndrome

Diagnosis of adrenogenital syndrome

Differential diagnosis of adrenogenital syndrome

Prognosis of adrenogenital syndrome

Treatment of adrenogenital syndrome

adrenogenital syndrome. Etiology, clinic, diagnosis, treatment.

AGS is a consequence of a congenital deficiency of enzyme systems involved in the synthesis of steroid hormones of the adrenal glands. This genetic defect has a recessive inheritance path; both men and women can be carriers of the defective gene.

Hyperproduction of androgens in the adrenal cortex in congenital AGS is a consequence of a gene mutation, a congenital genetically determined deficiency of the enzyme system. At the same time, the synthesis of cortisol, the main glucocorticoid hormone of the adrenal cortex, is disrupted, the formation of which decreases. At the same time, according to the feedback principle, the formation of ACTH in the anterior pituitary gland increases and the synthesis of cortisol precursors increases, from which androgens are formed due to enzyme deficiency. Under physiological conditions, androgens are synthesized in the female body in small quantities.

Depending on the nature of the deficiency of enzyme systems, AGS is divided into 3 forms, common symptom which is virilization.

AGS with salt wasting syndrome : deficiency of 3R-dehydrogenase leads to a sharp decrease in the formation of cortisol, resulting in frequent vomiting, dehydration of the body with impaired cardiac activity.

AGS with hypertension : deficiency of 11 (3-hydroxylase) leads to the accumulation of corticosterone and, as a result, to the development of hypertension against the background of impaired water and electrolyte metabolism.

AGS simple virilizing form : deficiency of C21-hydroxylase causes an increase in the production of androgens and the development of symptoms of hyperandrogenism without a significant decrease in the synthesis of cortisol. This form of AGS is the most common.

AHS with salt loss and hypertension is rare: 1 in 20,000-30,000 births. Both of these forms violate not only sexual development, but also the function of the cardiovascular, digestive and other body systems. Symptoms of AHS with salt loss appear in the first hours after birth, and the hypertensive form - in the first decade of life. These patients make up a contingent of general endocrinologists and pediatricians. As for the simple virilizing form of AGS, it is not accompanied by somatic developmental disorders.

Deficiency of C21-hydroxylase, despite its congenital nature, can manifest itself in different periods life; depending on this, congenital, pubertal and post-pubertal forms are distinguished. In congenital adrenogenital syndrome, the dysfunction of the adrenal glands begins in utero, almost simultaneously with the beginning of their functioning as an endocrine gland. This form is characterized by virilization of the external genital organs: an increase in the clitoris (up to a penis-shaped), the fusion of the labia majora and the persistence of the urogenital sinus, which is the fusion of the lower two-thirds of the vagina and the urethra and opens under the enlarged clitoris. At the birth of a child, gender is often mistaken - a girl with congenital AGS is mistaken for a boy with hypospadias and cryptorchidism. It should be noted that even with severe congenital AGS, the ovaries and uterus are developed correctly, the chromosome set is female (46 XX), since intrauterine hyperproduction of androgens begins at a time when the external genital organs have not yet completed sexual differentiation.

This form of AGS is characterized by hyperplasia of the adrenal cortex, in which androgens are synthesized. Therefore, its second name is congenital hyperplasia of the adrenal cortex. In the case of pronounced virilization of the external genital organs, noted at birth, this form is called false female hermaphroditism. This is the most common form of hermaphroditism in women among disorders of sexual differentiation).

In the first decade of life, girls with a congenital form of AGS develop a picture of premature sexual development according to the heterosexual type.

At the age of 3-5 years, under the influence of ongoing hyperandrogenism, girls develop a pattern of male-type PPR: virilous hypertrichosis begins and progresses, at 8-10 years old, rod hair appears on the upper lip and chin, "sideburns".

Due to the pronounced anabolic action of androgens, hyperandrogenism stimulates the development of muscle and bone tissues, there is a rapid growth of tubular bones in length, the physique, the distribution of muscle and adipose tissue acquires male type. In girls with congenital AGS, by the age of 10-12, the body length reaches 150-155 cm, the children no longer grow anymore, because. ossification of the growth zones of bones occurs. The bone age of children at this time corresponds to 20 years.

Diagnostics. For diagnosis, family history data are used (violation of sexual development in relatives, a combination of short stature with infertility, early deaths of newborns with an abnormal structure of the genitals). The clinical picture of the disease plays an important role in the diagnosis. Prenatal diagnosis is possible by determining the concentration of 17-hydroxyprogesterone in the amniotic fluid, as well as identifying a gene mutation.

From laboratory data, attention should be paid to an increase in the excretion of 17-KS in the urine, and in the blood serum - the level of 17-hydroxyprogesterone and ACTH. In the salt-losing form of AGS, in addition to the above changes, vomiting, dehydration, hypochloremia and hyperkalemia are detected.

Differential diagnosis. AGS must be differentiated from other forms of early puberty, growth acceleration, dwarfism, and intersexism. The salt-wasting form is also differentiated with pyloric stenosis, diabetes insipidus, i.e., with diseases that may be accompanied by dehydration. Also with PCOS.

Treatment and prevention. Treatment depends on the form of AGS. With a simple form, treatment with glucocorticoids is carried out throughout the life of the patient. Prednisolone is prescribed in a daily dose of 4 to 10 mg / m 2 of the body in 3-4 doses. Girls have to resort to surgical plastic surgery of the external genitalia at the age of 3-4 years. AT acute period the salt-losing form of the disease shows salt-replacing solutions (isotonic sodium chloride solution, Ringer's solution, etc.) and 5-10% glucose solution in a ratio of 1: 1 intravenously drip per day up to 150-170 ml per 1 kg of body weight. As a hormonal drug, it is preferable to hydrocortisone hemisuccinate (Solucortef) at a daily dose of 10-15 mg / kg, divided into 4-6 intravenous or intramuscular injections. In cases of stressful situations (intercurrent disease, trauma, surgery, etc.), the dose of glucocorticoids is increased by 1.5-2 times in order to avoid the development of acute adrenal insufficiency (hypoadrenal crisis). If therapy is carried out with prednisolone, then deoxycorticosterone acetate (DOXA) is simultaneously administered intramuscularly at a dose of 10-15 mg per day. In the future, the dose of DOXA is reduced, administered every other day or two.

With early and regular treatment, children develop normally. With the salt-wasting form of AGS, the prognosis is worse, children often die in the 1st year of life.